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Women With Certain Type of Ovarian Cancer and BRCA Gene Mutation Have Improved Survival at 5 Years

January 24 2012

 

CHICAGO – Among women with invasive epithelial ovarian cancer, patients having a germline (gene change in a reproductive cell that could be passed to offspring) mutation in the BRCAl or BRCA2 genes was associated with improved 5-year overall survival, with BRCA2 carriers having the best prognosis, according to a study in the January 25, 2012, issue of JAMA.

“Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 are the strongest known genetic risk factors for both breast and epithelial ovarian cancer (EOC) and are found in 6 percent to 15 percent of women with EOC,” according to background information in the article. “The relative prognosis of BRCA1/2 carriers and noncarriers is unclear.”

Kelly L. Bolton, PhD, of the National Cancer Institute, Bethesda, Md., and colleagues conducted a study to provide evidence of the relative effect of germline BRCAl and BRCA2 mutations on prognosis for women with epithelial ovarian cancer. The study consisted of a pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1,213 EOC cases with pathogenic germline mutations in BRCA1 (n = 909) or BRCA2 (n = 304) and from 2,666 noncarriers recruited and followed up at variable times between 1987 and 2010. During the 5 years following EOC diagnosis, 1,766 deaths occurred.

The researchers found that 5-year overall survival was 36 percent for noncarriers of the gene mutations, 44 percent for BRCA1 carriers, and 52 percent for BRCA2 carriers. In a model only adjusted for study site and year of diagnosis, BRCA1 carriers had a more favorable survival than noncarriers, which improved slightly after additional adjustment for stage, grade, histology, and age at diagnosis. BRCA2 carriers had a greater survival advantage compared with noncarriers, particularly after adjusting for other prognostic factors.

The survival advantage for BRCAl and BRCA2 carriers compared with noncarriers was present but less marked among women who reported a family history of ovarian, breast cancer, or both.

“Our study results have potentially important implications for the clinical management of patients with EOC. Most immediately, our findings can be used by health care professionals for patient counseling regarding expected survival. BRCAl and BRCA2 carriers with EOC respond better than noncarriers to platinum-based chemotherapies and have improved survival despite the fact that the disease is generally diagnosed at a later stage and higher grade. If patients could be stratified based on their BRCA status, their treatment could be tailored to reflect this, with noncarriers targeted for more aggressive treatments. Our data provide further support that there may be different functional mechanisms involved in the etiology of different subtypes of EOCs and, therefore, different therapeutic targets based on germline and somatic [changes to the genetics of a multicellular organism which are not passed on to its offspring through the germline] genetic variation,” the researchers write.

“… given the important prognostic information provided by BRCAl and BRCA2 status and the potential for personalized treatment in carriers, the routine testing of women presenting with high-grade serous EOC may now be warranted.”

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Genetic Abnormality Predicts Benefit from Treatment for a Rare Brain Tumor

Study shows doubling in survival time for patients with two different chromosomal deletions

January 19 2012

A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion. This abnormality is characterized by the simultaneous deletion of the short arm of chromosome 1 and long arm of chromosome 19. The presence of the chromosomal abnormality was associated with substantially better prognosis and marked improvements in survival in a treatment program of combined chemotherapy and radiation therapy compared to radiation therapy alone.  Oligodendrogliomas are characterized by tumors that form in the nerve tissue of the brain. The study was supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

In the trial, 286 patients with aggressive oligodendrogliomas were randomly assigned to study groups of equal size to receive radiotherapy alone or radiotherapy plus PCV chemotherapy, which includes the drugs procarbazine, lomustine and vincristine.  Tumor tissue from all patients was collected and stored for genetic tests.  The analysis was performed when about half of the patients had been followed for just over 11 years. 

Oligodendrogliomas occur primarily in adults, and the average age at diagnosis is 35.  The tumors comprise 9.4 percent of all primary brain and central nervous system tumors.

For the entire study population, the median overall survival time for patients receiving radiotherapy alone or radiotherapy plus PCV chemotherapy was similar. However, the 126 patients with 1p19q co-deleted tumors had much longer median survival times than the 135 patients whose tumors did not carry the 1p19q co-deletion: 8.7 years versus 2.7 years.  This observation suggests that patients whose tumors contain the chromosomal abnormality will live substantially longer than patients whose tumors don’t carry it, regardless of treatment.  Even more impressive, however, was the finding that 1p19q co-deletion predicted the benefit from adding chemotherapy to radiotherapy. Patients with 1p19q co-deleted tumors who received PCV chemotherapy plus radiotherapy (59 patients) had a median overall survival time of 14.7 years, compared with only 7.3 years for patients with co-deleted tumors who received radiotherapy alone (67 patients). Patients whose tumors did not have the chromosomal abnormality did not show an improvement in survival from the addition of chemotherapy.   

The study, known as RTOG 9402, was led by the Radiation Therapy Oncology Group (RTOG) with the participation of the North Central Cancer Treatment Group, the National Cancer Institute of Canada Clinical Trials Group, the Eastern Cooperative Oncology Group, and SWOG (formerly the Southwest Oncology Group).

“The Radiation Therapy Oncology Group and other participating cooperative groups are to be congratulated for conducting this randomized clinical trial in a rare form of brain tumor that took many years,” said Jeffrey Abrams, MD, associate director, Cancer Therapy Evaluation Program, NCI.  “Their persistence and dedication was rewarded as this genetic abnormality has a powerful effect on survival, and the results will change how patients with this disease are treated. This clinical trial also highlights the necessity for collecting tumor tissue for genetic studies to define more precisely the patients who benefit most from specific therapies.”

Currently, NCI is supporting two additional studies that attempt to improve on the treatment of these brain tumors.  Details on both studies can be viewed at:  
CODEL trial N0577 -- http://clinicaltrials.gov/ct2/show/study/NCT00887146?term=N0577&rank=1
CATNON trial RTOG 0834 -- http://clinicaltrials.gov/ct2/show/study/NCT00626990?term=rtog+0834&rank=1

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Study Showed Oxaliplatin Improved Colon Cancer Patient Survival

January 20 2012

Stage III colon cancer patients in the general population who receive adjuvant treatment for the disease have an improved rate of survival when oxaliplatin is added to 5-fluorouracil (5FU), according to a study published January 20, 2012, in The Journal of the National Cancer Institute.

Colon cancer is a leading global cause of both illness and death; with an estimated 101,340 cases among Americans in 2011. Roughly one‑third of diagnoses are stage III or node-positive disease.  In randomized clinical trials (RCTs), adding oxaliplatin to adjuvant 5FU is known to improve outcomes of patients with stage III colon cancer. But the effect of this combined therapy outside RCTs is unknown. In addition, fewer than 2% of patients with the cancer enroll in RCTs, and participants are known to be generally younger, healthier and less racially diverse than the overall cancer patient population.

In order to determine the effects of combined therapy in stage III colon cancer patients in the general population, Hanna K. Sanoff MD, and assistant professor of Medicine, Hematology and Oncology at the University of Virginia School of Medicine and colleagues, gathered data from patients using the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), among other cancer registries. All patients had stage III colon cancer, received chemotherapy within 120 days of surgery, and were age 75 years or younger. Overall survival (OS) was then compared between patients treated with combined therapy and standard chemotherapy.

The researchers found that adding oxaliplatin to adjuvant therapies for stage III colon cancer in patients of the general cancer population was just as effective as in patients from RCTs. The addition of oxaliplatin showed improved survival across various practice settings, including those with older and minority patients as well as patients with greater comorbidity. “Physicians and patients should be reassured from our findings that oxaliplatin is associated with marginally but consistently superior survival for patients diagnosed before age 75 years in community settings,” the authors write.  They feel that now that combined therapy has proven efficacious in the general population, it is important to home in on high –risk subgroups such as patients over age 75, racially diverse minorities, and those with co‑morbid conditions.

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Younger Breast Cancer Patients Have More Adverse Quality of Life Issues

January 20 2012

Younger women with breast cancer experience a decrease in their health-related quality of life (QOL), associated with increased psychological distress, weight gain, a decline in their physical activity, infertility and early onset menopause, according to a study published January 20, 2012, in the Journal of the National Cancer Institute.

Breast cancer is the most common non-skin cancer in women, and is the leading cause of death in women under 50 in the U.S.  While the survival rate for younger women with breast cancer has improved over the last two decades, their cancer treatments, despite their effectiveness, can seriously affect QOL and other health outcomes. 

To better understand the impact of cancer treatment on the quality of life of younger breast cancer survivors, Patricia A. Ganz, MD, director of cancer prevention and control research at the Jonsson Comprehensive Cancer Center at the University of California Los Angeles, and colleagues did a review of studies that focused on overall QOL, psychosocial effects, menopause and fertility-related concerns, and behavioral outcomes related to weight gain and physical activity. The studies were published between January 1990 and July 2010. Of the 840 titles and abstracts reviewed, they focused on 28 with the most relevant data. 

The researchers found that overall QOL was compromised in younger breast cancer survivors, with the mental issues more severe than the physical problems. Young women were also more depressed compared to the general age-matched population of women without cancer or women over 50 with breast cancer. Premature menopause, infertility and menopause-related symptoms were more common and contributing factors to the level of distress in women 50 or younger after treatment.  Weight gain and physical inactivity were common health outcomes in younger women, although exercise rates generally increased after treatment.  

The researchers write that in light of these adverse QOL outcomes, personalized treatment for breast cancer in younger women is particularly important. “By tailoring adjuvant therapy regimens and giving cytotoxic therapy only to those who may benefit, we can mitigate some of these side effects, but the long life expectancy for these younger women also provides a window of opportunity for cancer prevention and health promotion activities.”

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Studies Help Clarify the Role of Lapatinib (Tykerb) and Trastuzumab (Herceptin) in Treating HER2 Positive Breast Cancer

January 16 2012

In patients with HER2-positive breast cancer, Tykerb (lapatinib) has been used both in combination with herceptin (trastuzumab) and as an alternative single-agent therapy for pre-surgery (neo-adjuvant) chemotherapy treatment. Two new studies are published today on these drugs. One published by The Lancet Oncology, showing lapatinib to be less beneficial than trastuzumab for single-agent therapy, and one by The Lancet showing that combining both drugs appears almost twice as effective as single-agent therapy (although lapatinib causes more side-effects).

The human epidermal growth factor receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 15% of breast tumours and is associated with a poor outcome.

In The Lancet Oncology study, Professor Gunter von Minckwitz (German Breast Group, Neu-Isenburg, Germany), Prof. Michael Untch (AGO-Breast Study Group, Berlin, Germany), and colleagues did a randomised trial of lapatinib versus trastuzumab in 620 patients in Germany. All patients received a standard chemotherapy regimen plus either trastuzumab (309) or lapatinib (311). The primary outcome of the study was the proportion of patients achieving pathological complete response (pCR—the absence of any residual invasive cancer in the breast and absence of any metastatic cells in the regional lymph nodes). The researchers found that 30% of the trastuzumab group achieved a pathological complete response compared with 23% in the lapatinib group.

Side-effects were common in both groups. Chemotherapy with trastuzumab was associated with more swelling of legs (39% vs 29%) and shortness of breath (30% vs 21%), and lapatinib with more diarrhoea (75% vs 47%) and skin rash (55% vs 32%). Many more patients discontinued therapy due to toxic effects in the lapatinib group (33%) than in the trastuzumab group (14%). 70 serious adverse events were reported in the trastuzumab group and 87 in the lapatinib group.

The authors conclude: “This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2 treatment in combination with neoadjuvant chemotherapy.”

In a comment linked to The Lancet Oncology paper, Dr Stephen K Chia, Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada, says: “Moving forward into the future, no adjuvant (post-surgery) trials should be done without an adequate signal from preoperative trials showing safety, efficacy, target modulation, and, ideally, the identification of predictive biomarkers such that we no longer pick a loser to study in larger and more resource-intensive adjuvant trials.”

In The Lancet study, Dr José Baselga (Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA) and colleagues from the SOLTI group and Breast International Group did a randomised trial involving more than 400 women from 23 countries with HER2-postive breast cancer and tumours greater than 2 cm in diameter. 154 women received lapatinib, 149 trastuzumab, and 152 a combination of both treatments, all pre-surgery, with standard paclitaxel therapy added to each of these anti-HER2 regimens after 6 weeks.  Following a further 12 weeks of treatment, patients underwent surgery and then received the same anti-HER2 therapy for 1 year. The new aspect in this study is that patients received the same anti-HER2 therapy post-surgery as in the pre-surgery component, so eventually data will be available to study the correlation between pCR, the primary study endpoint, and disease free survival and overall survival.

The authors say: “Dual targeting of HER2-positive tumours with trastuzumab and lapatinib is undertaken because of primary and acquired resistance to both agents, their partly non-overlapping mechanisms of action, and the well characterised synergistic interaction between them in HER2 breast-cancer models.”

The research team found that the pCR rate was significantly higher in the group given combination treatment (51%) than in the group given trastuzumab alone (30%), a difference of 21%. No statistically significant difference in pCR between the lapatinib (25%) and the trastuzumab (30%) groups was recorded. No major cardiac dysfunctions occurred across the treatment groups (anti-HER2 therapy can cause cardiac toxicity). Frequency of grade 3 diarrhoea was far higher with lapatinib (23%) and lapatinib plus trastuzumab (21%) than with trastuzumab (2%). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (18%) and lapatinib plus trastuzumab (10%) than with trastuzumab (7%).

The authors conclude: “Overall, dual HER2 blockade could be an improved approach to treatment of patients with HER2-positive tumours. Our study shows that dual inhibition of HER2 by lapatinib and trastuzumab in combination with paclitaxel is better than single-agent targeting of HER2 in the neoadjuvant (pre-surgical) setting. Dual HER2 blockade might be a valid approach in patients with early HER2-positive disease.”

They add: “Our study also supports investigation of novel targeted agents for breast cancer in the neoadjuvant (pre-surgical)setting, when tumours have not yet acquired resistance to therapy and when chances of clinical benefit are highest.”

In a comment linked to The Lancet article, Professor Michael Gnant and Dr Guenther G. Steger, Medical University of Vienna, Austria, say trials such as this are convincing enough to consider different routes of evaluating drugs from a both a scientific and regulatory perspective. They say: “Trials in the neoadjuvant setting based on research-based hypotheses (after establishment of drug safety) could lead to a saving of enormous sums in drug development costs, and promising new drugs for treatment of early breast cancer could become available much more quickly than at present.”

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Researchers Find First Major Gene Mutation Associated with Hereditary Prostate Cancer Risk

Discovery may provide clues on disease development and who may need earlier screening

January 11 2012

After a 20-year quest to find a genetic driver for prostate cancer that strikes men at younger ages and runs in families, researchers have identified a rare, inherited mutation linked to a significantly higher risk of the disease.

A report on the discovery, published in the January 12, 2012 issue of the New England Journal of Medicine, was led by investigators at the Johns Hopkins University School of Medicine and the University of Michigan Health System. The research team found that men who inherit this mutation have a 10 to 20 times higher risk of developing prostate cancer.

While accounting for only a small fraction of all prostate cancer cases, the discovery may provide important clues about how this common cancer develops and help to identify a subset of men who might benefit from additional or earlier screening. This year, an estimated 240,000 men in the United States will be diagnosed with prostate cancer.

“This is the first major genetic variant associated with inherited prostate cancer,” says Kathleen A. Cooney, MD, professor of internal medicine and urology at the U-M Medical School, one of the study’s two senior authors.

“It’s what we’ve been looking for over the past 20 years,” adds William B. Isaacs, PhD, professor of urology and oncology at the Johns Hopkins University School of Medicine, the study’s other senior author. “It’s long been clear that prostate cancer can run in families, but pinpointing the underlying genetic basis has been challenging and previous studies have provided inconsistent results.” For this study, the researchers collaborated with John Carpten, Ph.D., at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona, who used the latest technology to sequence the DNA of more than 200 genes in a human chromosome region known as 17q21-22.

Cooney, working with Ethan Lange, PhD, of the University of North Carolina on the U-M Prostate Cancer Genetics Project, was the first to identify 17q21-22 as a region of interest.

Researchers started with samples from the youngest patients with prostate cancer in 94 families who had participated in studies at U-M and Johns Hopkins. Each of those families had multiple cases of the disease among close relatives, such as between fathers and sons or among brothers.

Members of four different families were found to have the same mutation in the HOXB13 gene, which plays an important role in the development of the prostate during the fetal stage and its function later in life. The mutation was carried by all 18 men with prostate cancer in these four families.

The researchers collaborated with Jianfeng Xu, PhD, and Lilly Zheng, PhD, at Wake Forest University to look for the same HOXB13 gene mutation among 5,100 men who had been treated for prostate cancer at either Johns Hopkins or U-M. The mutation was found in 1.4 percent—or 72 of the men. It turned out that those men were much more likely to have at least one first-degree relative, a father or brother, who also had been diagnosed. The researchers also looked for the mutation in a control group of 1,400 men without prostate cancer, and only one of those men carried the mutation. In addition, the researchers studied men who were specifically enrolled in studies of early-onset or familial prostate cancer.

“We found that the mutation was significantly more common in men with a family history and early diagnosis compared with men diagnosed later, after age 55, without a family history. The difference was 3.1 percent versus 0.62 percent, Cooney says.

“We had never seen anything like this before. It all came together to suggest that this single change may account for at least a portion of the hereditary form of the disease,” says study co-author Patrick Walsh, MD, professor of urology at Johns Hopkins, who is one of the pioneers in prostate cancer treatment. In the 1980s, Walsh was one of the first to publish a study showing that the risk of prostate cancer was higher among men with close relatives who also had the disease.

The researchers say with further study, it may be possible one day to have genetic test for inherited prostate cancer in much the same way that tests are available to look for BRCA1 and BRCA2 mutations that greatly increase a woman’s chance of developing breast and/or ovarian cancer.

“We need to continue studying this variant and look at larger groups of men. Our next step will be to develop a mouse model with this mutation to see if it causes prostate cancer,” says Isaacs. He adds, “Future DNA sequencing may also identify additional rare variants that contribute to prostate cancer risk in families.”

This particular mutation was found in families of European descent, while two different mutations on the HOXB13 gene were identified in families of African descent. Since only seven of the 94 families studied were of African descent, more research will be required before the significance of those mutations is known. African-American men are more likely to be diagnosed with prostate cancer at younger ages and have a more aggressive form of the disease.

Cooney says patients with questions about prostate cancer screening, particularly if the disease runs in their families, are encouraged to speak with their doctor.

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Study Evaluates Long-Term Health-Related Quality of Life in Head and Neck Cancer Survivors

January 16 2012

 

CHICAGO – Eating problems due to poor throat (oropharyngeal) functioning and persistent pain appear to be the most prevalent problems faced by long-term survivors of head and neck cancer, suggests a study published Online First by the Archives of Otolaryngology – Head & Neck Surgery, one of the JAMA/Archives journals.

The study by Gerry F. Funk, MD, University of Iowa Hospitals and Clinics in Iowa City, reports that over 50 percent of these survivors had problems eating, 28.5 percent reported depressive symptoms and 17.3 percent reported substantial pain. However, the average general health of the long-term survivors was equivalent to age-matched norms from the general population.

“Early interventions addressing eating issues, swallowing problems and pain management will be a crucial component in improving this patient population’s long-term QOL [quality of life], especially in those who are functioning poorly one year after diagnosis,” researchers conclude.

The study included 337 patients diagnosed with head and neck cancer between January 1995 and December 2004, who enrolled in the Outcomes Assessment Project and survived at least five years. Researchers note that relatively few studies have evaluated long-term health-related quality of life outcomes five or more years from diagnosis in patients with head and neck cancer.

Researchers highlight that their study, along with others, demonstrate that poor oral (mouth) and oropharyngeal (throat) function was a persistent problem in long-term survivors that can be due to neuromuscular changes, anatomic deficits after surgery, pain, dental deficits and other factors.

“In addition, poor swallowing function may exert more than a detrimental effect on HRQOL [health-related quality of life],” the study notes. Unrecognized aspiration after chemoradiation may contribute to death.

The study results also indicate that at long-term follow-up, 13.6 percent of the survivors continued to smoke and 38.9 percent used alcohol. Multivariate analyses shows that pain and diet in the first year were the strongest independent predictors of five-year, health-related quality of life outcomes.

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Predicting the Value of Indexing Symptoms for Ovarian Cancer

January 10 2012

The use of symptom indices to identify patients with symptoms associated with ovarian cancer who may need further screening is increasing in both the UK and the US in an attempt to promote earlier diagnosis, but they may need to be reassessed in order to help better detect cancer, according to a study published January 13, 2012, in the Journal of the National Cancer Institute.

Ovarian cancer is a disease which is perceived to rarely produce symptoms until the disease has spread to other organs of the body, allowing the disease to reach an advanced stage before it is caught. Some evidence suggests patient-reported symptoms may help detect the cancer early on, and in fact, the Goff index, which uses questionnaire data, has been reported to be effective in identifying women who are at a low to moderate risk of ovarian cancer. However, symptom assessment may greatly influence index performance.

To determine the effectiveness of the symptom indices, Anita Wey Wey Lim of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, at Queen Mary University of London and associates looked at data from 194 women who had recently been diagnosed with ovarian cancer and 268 control subjects who underwent ovarian cancer screenings.  The symptom data was assessed through questionnaires, telephone interviews, and general practitioner notes.  The sensitivity of the symptoms reported within a few months of the diagnosis was also determined by comparing two 12 month periods (0-11 and 3-14 months before diagnosis).

The researchers found that the results were similar to those found in previous reports on the Goff index and that the sensitivity of the symptoms were stronger in late- vs early-stage disease. The assessment also shows that there is only a slight variation in the symptoms reported by women with early- vs late-stage disease. 

The authors note that a strong point in the study comes from a comparison of multiple data sources, which had never been done before.  Even so, they write that, “The small differences between the three indices indicate that there is little to gain from deriving new symptom indices.”  They also suggest that while a symptom index could advance the diagnosis of ovarian cancer, the benefits of such are greatly overemphasized, given that most symptoms of the disease emerge within three months before diagnosis. They write, “At best, a symptom index might advance diagnosis of ovarian cancer by 3 months or more in two-thirds of women. For a more specific index, the sensitivity would be approximately one-third.”

In an accompanying editorial, Patricia Hartge, ScD, at National Cancer Institute’s Division of Cancer Epidemiology and Genetics, and James L. Speyer, MD, from the NYU Langone Cancer Center, write that symptom indices such as the Goff index and two novel indices described in the study are viewed as good for detecting early-stage ovarian cancer with the assumption that an early detection and therapy can achieve a better patient outcome. While this can be true, they caution that these indices were not highly specific and that the screeners found the cancer symptoms close to the time in which the patient was diagnosed. “The study design permits no calculation of years of life that might have been saved or lost if screeners actually were used—only a large and expensive randomized trial would do that—but clinical gains likely would be minor, and many women would undergo unnecessary diagnostic procedures to assure that they are cancer free.”  They also point out that the difficulty of detecting ovarian cancer early persists for various reasons. “The biology of ovarian cancer, the arithmetic of screening, and the clinical characteristics of the disease and its treatment collude to make it difficult to find ovarian cancer early enough to matter.”

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Targeted Therapy Extends Progression-Free Survival of Patients with Advanced Ovarian Cancer

December 28 2011

PHILADELPHIA – Targeted drugs, which block or disrupt particular molecules involved in the growth of tumors, have been shown to be effective treatments against many types of cancer. A new phase 3 clinical trial conducted by the Gynecologic Oncology Group (GOG) showed that a targeted therapy called bevacizumab (Avastin) effectively delayed the progression of advanced ovarian cancer. Patients with newly diagnosed advanced ovarian cancer now typically undergo surgery and chemotherapy, but the new research suggests an additional avenue of treatment. The results of the trial appear in the December 29, 2011, issue of the New England Journal of Medicine.

"This approach can be looked upon as a third major component of treatment for ovarian cancer and related malignancies," says Robert A. Burger, MD, lead investigator on the GOG study and director of the Women's Cancer Center at Fox Chase Cancer Center. "We've had the combination of surgical management and cytotoxic chemotherapy for many years, but we haven't really seen anything else in terms of a fundamental class of treatment. This represents a new way for us to control the disease."

The placebo-controlled study, which was sponsored by the National Cancer Institute, enrolled 1,873 patients with previously untreated advanced disease from 336 sites, primarily in the United States, but also in Canada, South Korea, and Japan. The patients either had stage III ovarian cancer that could not be entirely removed with surgery, or stage IV disease, and were randomly assigned to one of three groups. For patients who received bevacizumab with chemotherapy followed by bevacizumab for up to an additional 10 months, the median time until their cancer progressed was 14.1 months, compared to 10.3 months for patients in the control group, who received chemotherapy with a placebo and then continued with a placebo. The net effect was a 28% reduction in the risk of disease of ovarian cancer progression over time. Patients who received bevacizumab only with chemotherapy, but not afterward, had a median progression-free survival of 11.2 months.

The National Cancer Institute estimates that nearly 22,000 women were diagnosed with ovarian cancer in 2011, and more than 15,000 died of the disease. For patients diagnosed before the cancer has spread, the five-year relative survival rate is about 93 percent (relative survival measures survival of cancer only, independent of other causes of death). But ovarian cancer is insidious—early symptoms, like bloating, abdominal pain, and trouble eating, are typical of many illnesses and easily dismissed as non-threatening. Women often do not learn they have the disease until it's already spread. In 62 percent of new cases, the patient's cancer has metastasized to distant sites, and the five-year survival rate is just under 27 percent.

Bevacizumab is already FDA-approved for use against some types of colon, lung, kidney and brain cancers; its accelerated approval for metastatic breast cancer was recently revoked by the FDA. The drug acts by binding with vascular endothelial growth factor (VEGF), a protein produced by certain cancers that helps initiate the growth of new blood vessels that feed the tumor. The process of growing new blood vessels is called angiogenesis, and bevacizumab is an angiogenesis inhibitor.

”Bevacizumab blocks the growth factor VEGF, which is important in the process of ovarian cancer progression,” says Burger, “and we've seen that this drug is also active in patients with recurrent disease.”

Angiogenesis happens at the interface between the host and the disease, which makes it an appealing target for treatment, says Burger, who also led the Phase II GOG study on using bevacizumab in women with recurrent ovarian cancer. He says different ovarian cancers may appear identical under the microscope but differ biologically, which means they'll respond differently to treatment.

In the NEJM paper, Burger and his co-authors point out that another ovarian cancer trial conducted primarily in Europe called ICON7 demonstrated positive results in using becavizumab in combination with chemotherapy and then continued for up to 7 months.

Co-authors on the NEJM paper include Mark F. Brady, Roswell Park Cancer Institute; Michael A. Bookman, Arizona Cancer Center; Gini F. Fleming, University of Chicago; Bradley J. Monk, Creighton University School of Medicine; Helen Huang, Roswell Park; Robert S. Mannel, University of Oklahoma Health Sciences Center, Oklahoma City; Howard D. Homesley, Wake Forest University School of Medicine; Jeffrey Fowler, James Cancer Hospital at the Ohio State University, Hilliard; Benjamin E. Greer, Seattle Cancer Care Alliance; Matthew Boente, Minnesota Oncology and Hematology; Michael J. Birrer, Harvard Medical School and Massachusetts General Hospital; and Sharon X. Liang, North Shore–Long Island Jewish Health System.

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Most Parents Who Get Tested for Breast Cancer Genes Share Results with their Children

January 09 2012

A new study has found that when parents get tested for breast cancer genes, many of them share their results with their children, even with those who are very young. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study also revealed that most parents think that their children are not distressed when they learn about the test results.

For parents, one of the primary motivations for getting tested for hereditary cancer genes is to better understand the risk that their children face; however, many parents struggle with the decision of whether, and when, to tell their minor children the results of such tests. To help determine what factors make parents more or less likely to report their test results to their children, Angela Bradbury, MD, of the Fox Chase Cancer Center in Philadelphia, and her colleagues interviewed 253 parents who had genetic testing for mutations in two common breast cancer–related genes (BRCA1 and BRCA2) that can be inherited. All parents had children under the age of 25 at the time of the genetic test. The investigators asked parents whether they told their children their test results, and if they did, how they felt their children reacted to the information.

Genetic testing revealed that 29 percent of parents had a BRCA gene mutation that confers an increased risk of developing breast cancer. The majority of parents in the study shared their results with at least one of their children. (Among 505 children, 334 [66 percent] learned of their parents’ test results.) Parents were more likely to report their results to older children; however, about half of ten to 13 year olds, and some even younger children were told of their parents’ test results. Also, parents were more likely to share negative test results—meaning no mutation was found—particularly if the child was female. Most of the parents reported that test results did not appear to distress their children, although distress was more likely when the test revealed a mutation in one of the breast cancer genes and when the child was under ten years old.

“We know that adolescence is a time when children establish many important health behaviors they continue in adulthood. An understanding about children’s reactions to these communications may assist parents in their decisions about whether, or when, to share their genetic test results,” said Dr. Bradbury. “This could also help parents begin conversations with their children that can encourage them to adopt healthy behaviors but not cause them distress,” she added. Such early conversations about cancer risk may provide parents with opportunities to promote protective health behaviors—such as eating a healthy diet and not smoking—that could help keep their children cancer-free.

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Study Shows No Evidence of a Mortality Benefit to PSA Screening

January 06 2012

Men enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial had no evidence of a mortality benefit compared to a control group of men undergoing usual care, according to a study published online January 6, 2012, in the Journal of the National Cancer Institute. 

The Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) Trial is a multi-center, two-arm trial, which began enrollment in November 1993 with follow-up through December 2009, and was designed to evaluate the effect of screening on these specific cancers. The enrollees were aged 55-74 and had no previous personal history of these cancers. Men in the intervention arm underwent annual PSA testing for six years and annual digital rectal examination for four years, while those in the control arm received their usual medical care, which for some men included screening.

A previous report of PLCO results through ten years was criticized for being too short of a follow-up period.  To determine longer-range outcomes among the men enrolled in PLCO, Gerald L. Andriole, MD, of Washington University School of Medicine in St. Louis, and colleagues, examined outcomes of the men through 13 years. The researchers found a statistically significant 12% relative increase in the incidence rate of prostate cancer, and a non-statistically significant decrease in the incidence of high-grade prostate cancer in the intervention arm compared to the control arm, but no difference in mortality between the two arms.  In addition, there was no apparent differential effect of screening by age category, pre-trial PSA testing, or co-morbidity. 

The authors write, “Improvements in prostate cancer treatment are probably at least in part responsible for declining prostate cancer mortality rates. Even if life is only prolonged by therapy, the opportunities for competing causes of death increase, especially among older men.”

The authors also point out that of the 4250 prostate cancer case patients diagnosed in the intervention arm, 455 (10.7%) died of causes other than the cancer types studied; in the control arm, 3815 men were diagnosed with prostate cancer of whom 377 (9.9%) died, also of other causes. “Thus, a higher percentage of deaths from other causes rather than a deficit occurred among the prostate cancer patients diagnosed in the intervention arm, an indication of the over-diagnosis associated with PSA detection,” the authors write.

The researchers plan to again update the mortality findings from the prostate component of the PLCO after follow-up data through 15 years becomes available.

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Removal of Lymph Nodes During Surgery for Thyroid Cancer May Be Beneficial

Procedure may reduce recurrence rates, lower tumor marker levels

December 20 2011

Papillary thyroid cancer accounts for the majority of all thyroid malignancies, which primarily impact women. A new study indicates that routinely removing lymph nodes in the neck in these cancer patients may help prevent the disease from coming back. 

When thyroid cancer metastasizes, lymph nodes in the neck may be affected, but these lymph-node tumors can be tiny and may not be detected by ultrasounds done before surgery to remove the diseased thyroid — or even during the procedure itself.   

In an international academic study published in the December issue of the journal Surgery, UCLA researchers and colleagues demonstrate that routine removal of neck lymph nodes during initial thyroid surgery for papillary cancer may lead to lower disease recurrence rates and lower levels of thyroglobulin, a thyroid tumor marker that can be an indicator of disease when elevated. 

Although it is standard procedure in some cancer centers, there has been debate in the worldwide surgical community about the benefits of routinely removing neck lymph nodes, a procedure known as prophylactic central neck lymph-node dissection, or CLND. 

"We found that re-operation rates due to cancer were lower in patients who had routine removal of these lymph nodes, which suggests a more thorough surgical clearance of disease," said the study's senior author, Dr. Michael Yeh, an associate professor of surgery at the David Geffen School of Medicine at UCLA. "Our findings may help add to growing evidence that this additional procedure, performed during initial thyroid surgery, may be helpful in management of papillary thyroid cancer."

For the study, researchers examined data on 606 patients who received care in one of three endocrine surgical units in the U.S., England and Australia. Patients were divided into two groups: Group A patients had undergone total thyroid removal alone; Group B patients had undergone both thyroid removal and dissection of central neck lymph nodes. Patients were followed for an average of three-and-a-half years following surgery. 

The standard pre-operative evaluation of all patients included a fine-needle biopsy of the primary thyroid tumor and determination of neck lymph-node disease status through physical examination and ultrasound of the neck. 

The rate of disease recurrence in the entire study population was 6.9 percent. The researchers found that the need for central neck re-operation was significantly lower among patients who had undergone the routine initial central neck lymph-node dissection, compared with those who had undergone only thyroid removal (1.5 percent vs. 6.1 percent). 

Stimulated thyroglobulin levels were also lower among patients in Group B, which may demonstrate a more thorough clearing of disease in the patients who had both thyroid and neck lymph-node removal procedures, the researchers said. 

"This significant reduction in the need for further surgery in the critical central area of the neck is important, since it reduces risk to the many vital structures housed here, such as the nerves supplying the voice," said study co-author Dr. Mark Sywak of the University of Sydney in Australia. 

UCLA's Yeh noted that blood thyroglobulin levels are a useful and sensitive measure in tracking disease recurrence, especially when many tumors in this area are too tiny to be detected using a physical exam or ultrasound. 

Rates of temporarily low calcium levels, a common side effect, were significantly higher in Group B patients (9.7 percent), who had neck lymph nodes removed, than in Group A patients (4.1 percent) who had thyroid-removal surgery alone. The rate of long-term complications was low for both groups — about 1 percent. 

The researchers said the next step may be to conduct a prospective, randomized clinical trial to further assess the impact of routinely removing central neck lymph nodes during initial surgery for papillary thyroid cancer.  

The study took place at UCLA Medical Center; the University of Sydney, Australia; and Hammersmith Hospital at Imperial College London. 

Other study authors included Aleksandra Popadich, James C. Lee, Stan Sidhu, Leigh Delbridge and Mark Sywak from the University of Sydney endocrine surgical unit; Olga Levin and Kevin Ro, both students at the David Geffen School of Medicine at UCLA; Stephanie Smooke-Praw from the department of medicine at the Geffen School of Medicine; Maisam Fazel, Asit Arora, Neil S. Tolley and F. Fausto Palazzo from the department of thyroid and endocrine surgery at Hammersmith Hospital in London; and Diana L. Learoyd from the department of endocrinology at Royal North Shore Hospital in New South Wales, Australia. 

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Statement by American Society of Clinical Oncology CEO Allen S. Lichter, MD on the 40th Anniversary of the National Cancer Act

December 13 2011

ASCO thanks those in the U.S. Senate who today reaffirmed the value of cancer research by honoring the National Cancer Act of 1971. Forty years after that landmark legislation, ASCO urges members of both houses of Congress to help sustain the nation's commitment to conquer cancer through continued research. Federal research investments spurred by the Act enabled the nation to make tremendous progress in the prevention, early detection and treatment of cancer. Publicly-funded cancer research has also vastly increased our biological understanding of the disease.

Thanks to our nation's concerted effort to fight cancer, we've achieved substantial reductions in the cancer death rate and have pushed five-year survival rates for breast, testicular, and some childhood cancers to over 90 percent. The knowledge gained though NCI and NIH research on chemotherapy and targeted treatments, radiation therapy, surgical advances, and side effect management has improved care and helped achieve an 18 percent decrease in the cancer death rate since the 1990s. The 12 million cancer survivors in the country today are the true testament to the value of this research.

In spite of the great progress, we must push even harder moving forward. Let's renew the commitment to conquer a disease that continues to take too large of a toll on patients and is predicted to be a leading cause of death in the years to come.

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Childhood Cancer Survivors’ Exposure to Chemotherapy, Radiation Does Not Increase Risk of Birth Defects in their Children

December 12 2011

A study published online in the Journal of Clinical Oncology finds that children of childhood cancer survivors do not have an increased risk for birth defects – despite the fact that their parents received treatment with radiation and/or certain forms of chemotherapy that can damage the DNA of cancer cells and healthy cells alike. The findings provide reassurance to cancer survivors about the potential effects of their own treatment on their children, and help guide family planning.

A large, retrospective study shows that children of childhood cancer survivors who received prior treatment involving radiation to testes or ovaries and/or chemotherapy with alkylating agents do not have an increased risk for birth defects compared to children of survivors who did not have such cancer treatment. The findings provide reassurance that increased risks of birth defects are unlikely for cancer survivors who are concerned about the potential effects of their treatment on their children, and can help guide family planning choices.

“We hope this study will become part of the arsenal of information used by the physicians of childhood cancer survivors if reproductive worries arise,” said lead author Lisa Signorello, ScD, associate professor of medicine at Vanderbilt University in Nashville, TN, and senior epidemiologist at the International Epidemiology Institute in Rockville, MD. “Childhood cancer survivors face real reproductive concerns, including unknowns related to the effects of therapy. But, hopefully this study will provide some reassurance that their children are unlikely to be at increased risk for genetic defects stemming from their earlier treatment.”

According to Signorello, childhood cancer patients frequently receive aggressive, though life-saving, radiation and chemotherapy treatments that can affect their ability to have children. For girls, radiation to the pelvis – and the resulting damage to the uterus – has been associated with a risk for pregnancy outcomes such as miscarriage and preterm birth, and effects on the ovaries can lead to infertility. Radiotherapy and chemotherapy with alkylating agents (e.g., busulphan, cyclophosphamide and dacarbazine) are DNA-damaging treatments, affecting both cancer and healthy cells. Studies to date have not adequately addressed the question of whether genetic damage from a parent’s treatment could be passed down to their offspring. Genetic-based birth defects are rare in the general population (about 3 percent), and while previous research results indicated little or no increased risk for birth defects among the offspring of cancer survivors, such studies were relatively small in size and lacked detailed information about radiation and chemotherapy treatments, such as specific radiation doses to the testes and ovaries.

In the current study, investigators used information from the Childhood Cancer Survivor Study, a large retrospective study of treatment and outcomes in more than 20,000 childhood cancer survivors diagnosed between 1970 and 1986. Signorello and her colleagues examined data from 4,699 children of 1,128 men and 1,627 women who were 5-year childhood cancer survivors. The survivors reported their children’s health problems through questionnaires, and investigators also examined medical records from survivors and their children, focusing on survivors’ history of radiation to the testes or ovaries and chemotherapy with alkylating agents.

Of the survivors, 63 percent (1,736) had received radiation for their cancer as children, and 44 percent of men (496) and 50 percent of women (810) had received chemotherapy with alkylating agents. Overall, 2.7 percent (129) of the survivors’ children had at least one birth defect, such as Down syndrome, achondroplasia or cleft lip. Researchers found that 3 percent of children of mothers exposed to radiation or treated with alkylating chemotherapy agents had a genetic birth defect, compared to 3.5 percent of children of mothers who were cancer survivors but did not have such exposures. Only 1.9 percent of children of male cancer survivors who received these DNA-damaging treatments had such birth defects, compared to 1.7 percent of children of male survivors who did not have this type of chemotherapy or radiation. The researchers concluded that children of cancer survivors were not at higher risk for birth defects stemming from parents’ exposure to chemotherapy and/or radiation.

The researchers also noted that a strength of their study is the comparison they made to the children of other cancer survivors and not to the children of people randomly sampled from the general population. Signorello said that comparing cancer survivors to individuals in the general population can be difficult because the latter may not be as thorough in reporting health problems of their children, and the children of cancer survivors may be under heightened clinical surveillance and may appear to have higher rates of birth defects as a result. The investigators did, however, find that the overall prevalence of birth defects among the cancer survivors’ children was very similar to what has been reported in the general population.

The study is among the largest to examine birth defects in children of childhood cancer survivors, and among the first to evaluate birth defects using medical records to validate both the children’s health problems and the parents’ radiation and chemotherapy exposures.

“The possibility of birth defects in offspring has been a lingering concern among cancer survivors because it’s hard to address,” Signorello said. “We know these are rare outcomes, and a large study group was needed to address these questions. It took years to validate the parents’ self-reported outcomes, and to assemble and use the medical records of radiation and chemotherapy treatment exposures to allow us to quantify their exposure doses. These are the strongest results to date, adding greater certainty to other studies examining this common concern among survivors of childhood cancer.”

The researchers would like to continue to sequence the DNA of families of childhood cancer survivors (survivors and their children) to see if there is any evidence of radiation- or chemical-induced genetic damage, even if the children did not have birth defects. They would also like to combine data from all U.S. and international studies on this topic in order to provide even larger, more definitive results.

To view a full copy of the study, click here.

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Cancer Survivors Have Increased Risk of Cutaneous Melanoma

December 19 2011

CHICAGO – Patients with a previously diagnosed cancer have an increased risk of having cutaneous melanoma, with the highest risk among patients with prior diagnosis of melanoma, according to a report in the December issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Cutaneous melanoma (CM) is one of the most aggressive forms of skin cancer. It is the fifth most commonly diagnosed cancer among U.S. men and the seventh most commonly diagnosed cancer among U.S. women. The incidence of CM is increasing and death rates from the disease have not significantly diminished, according to background information in the article. The greatest risk factor for CM development is UV radiation exposure, though this risk is affected by patients’ race and genetics.

Geoffrey B. Yang, BS, a medical student at Case Western Reserve School of Medicine, Cleveland, Ohio, and colleagues analyzed data from the Surveillance, Epidemiology, and End Results database (1988-2007) to understand the risk of cutaneous melanoma following a previous cancer. The study included 70,819 patients with CM as a first primary cancer (median age of 54 years at the time of melanoma diagnosis) and 6,353 patients with CM (median age 70 years at the time of melanoma diagnosis) following a previous cancer.

The greatest number of melanomas developed among patients with a previous melanoma diagnosis – a finding consistent with other studies. Among patients younger than 45 years at first cancer diagnosis, 777 developed CM, with significantly higher risks among those with prior CM, other skin cancer, Kaposi sarcoma, female breast cancer and lymphoma. Patients 45 years of age or older at first cancer diagnosis had significantly higher risk of developing CM following prior CM, other skin cancers, ocular melanoma, female breast cancer, prostate cancer, lymphoma and leukemia.

“Characteristics associated with better survival in both cohorts included female sex, age younger than 45 years at melanoma diagnosis, being married, being white vs. black, decreasing Breslow depth [how deeply tumor cells have invaded], lack of tumor ulceration, no nodal involvement, and absence of metastases [the spread of cancer from the primary tumor to other locations in the body],” the authors write.

“Given that cutaneous melanoma is the most common second primary cancer in patients with a first CM (a risk that remains elevated for over 15 years), our results suggest the need for continued skin surveillance in melanoma survivors,” they conclude.

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Most Cancer-related Blood Clots Occur in Outpatients

December 12 2011

In a study of nearly 18,000 cancer patients, University of Rochester Medical Center researchers found that when blood clots develop – a well-known and serious complication of cancer treatment – 78 percent of the time they occur when a person is out of the hospital, at home or elsewhere, while on chemotherapy.

This data is striking because, until now, outpatients had not been systematically studied and previous data gathered on the incidence of blood clots was mostly from hospitalized patients, who tend to be sicker. However, with a shift toward outpatient cancer treatment, future efforts to prevent blood clots should focus on helping patients to avoid complications so they can continue to live fully, by working, raising children, and exercising, during cancer care, said Alok Khorana, MD, associate professor in the James P. Wilmot Cancer Center at URMC, and an international authority on venous thromboembolism or VTE.

“One in five patients develops blood clots after a cancer diagnosis and we believe that number is rising,” Khorana said. “The Surgeon General recently issued a Call to Action to reduce VTE. At this point public health efforts have focused on inpatient prophylaxis. These new data suggest that to reduce the burden of VTE in cancer patients, prevention efforts will have to shift to the outpatient arena as well.”

The cost of care for patient with blood clots was twice as high compared to patients who did not have that complication, Khorana also reported.

Khorana was invited to present his data at the 2011 ASH (American Society of Hematology) annual meeting in San Diego, attended by approximately 20,000 physicians and scientists. The scientific abstracts with the highest impact, including Khorana’s, were selected for platform talks.

Khorana and his research team conducted a retrospective, observational study between 2005 and 2009 from healthcare claims databases, which they believe is the largest population study of this kind. The databases provided both inpatient and outpatient information. Of the 17, 784 cancer patients identified, 5.6 percent developed blood clots, the study said. Of those who suffered from the complication, 21 percent had recently been hospitalized but 78.3 percent were being treated on an outpatient basis.

The medical term venous thromboembolism is a mass of red blood cells, clotting proteins and platelets that block the normal flow of blood. Clots form most often in the legs, lungs, or abdomen, and are life-threatening if not treated.

Cancer patients are more prone to blood clots for many reasons: the malignancy itself can secrete proteins associated with blood clots; several treatments (including surgery, chemotherapy, and hormonal therapy) raise the clot risk; decreased mobility due to active disease or hospitalization; a genetic predisposition; or having other health problems, such as infections, obesity, anemia, and lung disorders. And once a blood clot occurs, a cancer patient is much more likely to have other clots later.

“Ongoing public health issues that we must address are how to educate patients on the importance of blood clot prevention, and improving compliance to preventive treatment,” he said. Patients should immediately report to their physicians any unusual symptoms such as swelling or redness in limbs, or shortness of breath, even if they are otherwise feeling well.

For years Khorana and colleagues at URMC have been at the forefront of studying cancer-related blood clots, which is the second leading cause of death in this population.

The Rochester group published a risk model in the journal, Blood, and based partly on research from the group, the American Society of Clinical Oncology in 2007 issued its first set of guidelines for clinicians for the prevention of blood clots in cancer patients. Chief collaborators include Charles W. Francis, MD, professor of Medicine in Hematology/Oncology at the Wilmot Cancer Center, and Mark B. Taubman, MD, a cardiologist, researcher, and dean of the UR School of Medicine and Dentistry.

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Breast Cancer Survivors Struggle with Cognitive Problems Several Years after Chemotherapy or Radiation

December 12 2011

A new analysis has found that breast cancer survivors may experience problems with certain mental abilities several years after treatment, regardless of whether they were treated with chemotherapy plus radiation or radiation only. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that there may be common and treatment-specific ways that cancer therapies negatively affect cancer survivors’ mental abilities.

Previous research suggests that chemotherapy can cause problems with memory and concentration in breast cancer survivors. To compare the effects of different types of cancer treatment on such mental abilities, Paul Jacobsen, PhD, of the Moffitt Cancer Center and Research Institute in Tampa, and his colleagues examined 62 breast cancer patients treated with chemotherapy plus radiation, 67 patients treated with radiation only, and 184 women with no history of cancer. Study participants completed neuropsychological assessments six months after completing treatment and again 36 months later, which is further out from the end of treatment than most previous studies of this type.

The study confirmed that chemotherapy can cause cognitive problems in breast cancer survivors that persist for three years after they finish treatment. In addition, the investigators found that breast cancer survivors who had been treated with radiation (and not chemotherapy) often experienced problems similar to those in breast cancer survivors treated with both chemotherapy and radiation. They did not find that hormonal therapy (such as tamoxifen) caused cognitive difficulties.

“These findings suggest that the problems some breast cancer survivors have with their mental abilities are not due just to the administration of chemotherapy,” said Dr. Jacobsen. “Our findings also provide a more complete picture of the impact of cancer treatment on mental abilities than studies that did not follow patients as long or look at mental abilities in breast cancer survivors who had not been treated with chemotherapy,” he added.

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Report Identifies Steps that May Reduce Women's Risk for Breast Cancer Associated with Environmental

December 07 2011

WASHINGTON — Women may be able to reduce their risk for breast cancer by avoiding unnecessary medical radiation, forgoing use of combination estrogen-progestin menopausal hormone therapy if possible, limiting alcohol consumption, maintaining a healthy weight, exercising regularly, and avoiding tobacco use, says a new report from the Institute of Medicine. These preventive steps focus on the environmental risk factors for which there is consistent scientific evidence of an association with breast cancer.

The evidence also indicates a possible, though currently less clear, link to increased risk for breast cancer from exposure to benzene, 1,3-butadiene, and ethylene oxide, which are chemicals found in some workplace settings and in gasoline fumes, vehicle exhaust, and tobacco smoke. Avoiding personal use of hair dyes and non-ionizing radiation emitted by mobile devices and other technologies likely will not impact a woman's risk for breast cancer, as multiple studies have found no connection to the disease.

Because of insufficient or contradictory evidence, the scientific jury is still out on whether many chemicals of concern, including bisphenol A (BPA), pesticides, ingredients in cosmetics and dietary supplements, and other substances alter the risk for breast cancer, the report says. Women may choose to minimize their exposure to some chemicals, but the committee found the research inadequate to draw conclusions about the potential benefit of such actions. Chemical ingredients in cosmetics, dietary supplements, and other products undergo only very limited testing before they are put on the market, and the committee noted the value of efforts to help consumers become more aware of this issue.

The steps identified in the report have the potential to reduce risk for breast cancer among women in general, but the committee cautioned that the evidence on how much risk reduction any of these steps offers is inconclusive. Whether it is small or significant, the impact on individuals will vary considerably because women are exposed to a range of substances throughout their lives; in addition, biological, physical, and genetic factors influence their individual chances for developing the disease.

The report's conclusions are the result of a detailed review of scientific research on environmental factors that may affect breast cancer risk. The committee also explored challenges to studying possible links between environmental exposures and breast cancer and recommends future research directions. Areas where there is provocative but as yet inconclusive evidence and that warrant priority attention include overnight shift work and accompanying disruptions of the sleep cycle; chemicals that mutate genes, alter gene expression, or affect hormones such as estrogen; and gene-environment interactions. More research needs to be conducted on the effects of exposures throughout the entire life span, including at specific stages of breast development, and on the cumulative effects of exposures at different life stages or multiple exposures that occur together, the report emphasizes. Most research has focused on adults and on exposures occurring within a few years prior to a diagnosis, but recent studies have shown the importance of exposures at various life stages, such as childhood, adolescence, pregnancy, and menopause.

In many cases, more information also needs to be gathered to determine whether preventive steps can be taken and how they can be most effective. For example, we do not yet know when weight loss is most likely to be beneficial in reducing postmenopausal cancer risk.

"Breast cancer develops over many years, so we need better ways to study exposures throughout women's lives, including when they are very young," said committee chair Irva Hertz-Picciotto, professor, department of public health sciences, and chief, division of environmental and occupational health, School of Medicine, University of California, Davis. "We also need improved methods to test for agents that may be contributing to breast cancer risk and to explore the effects of combined exposures."

The study was sponsored by Susan G. Komen for the Cure. Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. For more information, visit http://national-academies.org or http://iom.edu.

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American Society of Clinical Oncology Issues Annual Report on Progress Against Cancer

Report Highlights the Year’s Most Significant Developments in Cancer Research, Policy

December 05 2011

ALEXANDRIA, Va. — The American Society of Clinical Oncology (ASCO) today released Clinical Cancer Advances 2011: ASCO’s Annual Report on Progress Against Cancer, an independent review of the advances in cancer research that have had the greatest impact on patient care this year. The report also identifies the most promising trends in oncology and provides insights from experts on where the future of cancer care is heading.

“We’ve made significant strides in clinical cancer research over the past year and this report adds renewed hope for patients,” said Nicholas J. Vogelzang, MD, Co-Executive Editor of the report. “More personalized treatment approaches and advances in early detection are helping patients live longer, healthier lives. But we must improve the nation’s clinical research system and expand access to quality cancer care to accelerate the pace of progress.”

This year’s top research advances demonstrate new therapies for reducing cancer recurrence, progress made against hard-to-treat cancers, and improvements in cancer prevention and screening. The report also highlights several new drug approvals that bring smarter, more effective therapies to specific genetic subgroups of patients with cancer. The top five advances selected by the editors are:

• A Phase III study finding that vemurafenib (Zelboraf), which targets a common mutation in melanoma in a gene called BRAF, improved overall survival in patients with advanced melanoma when compared to standard chemotherapy
• A large national screening trial of more than 50,000 current and former heavy smokers that found three annual low-dose computed tomography (CT) scans reduced the death rate from lung cancer by 20 percent compared to those who were screened with three annual chest X-rays
• FDA approvals on therapies for two hard-to-treat cancers:
  • Crizotinib (Xalkori) was approved for patients with advanced non-small-cell lung cancer who harbor a specific type of alteration in the anaplastic lymphoma kinase (ALK) gene based on the results from two Phase II studies: one study demonstrated that 50 percent of patients experienced complete or partial tumor shrinkage for a median of 10 months and a second study found a 61 percent objective response rate lasting a median of 12 months
  • Ipilimumab (Yervoy) – an immune therapy that activates the immune system’s T cells – was approved for patients with previously untreated metastatic melanoma based on the results of a Phase III trial showing that the drug, combined with the standard chemotherapy drug dacarbazine, improved overall survival by two months
• The first conclusive evidence that an aromatase inhibitor reduced the risk of a first breast cancer, making exemestane (Aromasin) a preventative treatment option for postmenopausal women who are at high risk for the disease

Selected by an 18-person editorial board of prominent oncologists, the report highlights a total of 54 advances in clinical oncology over the past year and covers the full scope of patient care, including cancer disparities, advanced cancer care and survivor care.

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Panel Endorses Active Monitoring and Delay of Treatment for Low-risk Prostate Cancer

Urges further research to clarify management strategies

December 07 2011

An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.

“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.

Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.

Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.

The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.

Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease,” stated Dr. Ganz.

The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.

The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.

With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.

An updated version of the panel's draft statement, which incorporates public comments received in an open conference, can be found at http://consensus.nih.gov.

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Risk of Second Cancer in Cancer Survivors Mainly Confined to the Same Cancer Type as the First

November 28 2011

Cancer survivors have more than double the risk of a second primary cancer of the same type, according to a study published in CMAJ (Canadian Medical Association Journal), whereas the risk of a second primary cancer of another type was only slightly elevated.

Danish researchers looked at data for the entire population of Denmark (7 49 705 people) from 1980 to 2007 to determine whether the risk of secondary cancer is linked to the type of cancer found in the first instance. About 10% — 765 255 people — had one or more diagnoses of primary cancer for a total of 843 118 diagnoses.

About 15% of cancer survivors worldwide are diagnosed with a second primary cancer.

The researchers found a 2.2-fold risk of a second primary cancer of the same type as the first in cancer survivors. The risk of a different type of second primary cancer was 1.1-fold. Risk varied depending on the type of cancer. The risk of a second cancer of the same type was reduced after prostate cancer and greatest after sarcoma. The risk of a second cancer of a different type was also reduced after prostate cancer and greatest after larynx cancer.

To understand the association between cancers, the researchers produced a table containing estimates of risk for all 27 cancers after all 27 first cancer types. They suggest that this catalogue might be valuable to further cancer studies.

“The striking contrast between the 2.2-fold increased risk of a second primary cancer being the same type as the first and the 1.1-fold increased risk of it being different from the first cancer suggests that characteristics of the individual patient were involved,” writes Dr. Stig Bojesen of Herlev Hospital, Copenhagen University Hospital and the University of Copenhagen, with coauthors. “The risk of a second primary cancer seems to be specific to cancer type and is probably driven by the patient’s genetic and lifestyle risk factors.”

They also looked at the association of the first cancer to smoking because it is known to increase the risks of many types of cancer. “We were surprised to see that in our study, the risk of other smoking-related cancers in patients surviving a smoking-related cancer was only 1.2-fold,” said Dr. Bojesen. “The good news is that in the individual cancer survivor, the increased risk of a new cancer is mainly confined to the same cancer as the first — even in people with an unhealthy lifestyle such as smoking.”

“We speculate that in general, risk factors acting over the long term seem to be type specific in the individual patient,” write the authors. “However, other explanations are also plausible: effects of treatment and an increase (or decrease) in diagnostic surveillance could change observed risk of cancer in the same organ as opposed to other organs.”

“Future studies of individual pairs of first and second primary cancers should clarify whether the association is due to shared genetic or lifestyle risk factors, codiagnosis of a primary cancer in close anatomic proximity to the first cancer, treatment of the first cancer or the timing of the diagnosis of the first cancer (in childhood v. adulthood),” the authors conclude.

In a related commentary, Dr. Marcy Winget from Alberta Health Services and coauthor write, “Nielsen and colleagues found that the risk of a second primary cancer depended greatly on the types of the first and second cancers; heterogeneity in risk was substantial across cancer types, regardless of whether the second cancer was the same type as the first.” They point out that this significant heterogeneity requires looking at risk for specific cancers by paired first and second cancers rather than overall risk.

“Caution must be exercised, however, in interpreting the findings for implications for clinical practice, in view of the substantial heterogeneity in risk.”

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Hospital Readmissions After Colon Surgery Common, Costly - and Preventable

Johns Hopkins researchers find nearly one in four patients readmitted within 90 days at a cost of $300 million a year

November 11 2011

Nearly one-quarter of privately insured colon surgery patients are readmitted to the hospital within three months of discharge at a cost of roughly $9,000 per readmission, according to Johns Hopkins researchers, who’ve identified a major area for quality improvement and cost reduction in health care.

The most common reason for returning to the hospital: complications from surgical-site infections, which are likely preventable, they say.

Readmission rates, an increasingly popular yardstick by which hospitals are judged and penalized by insurers, are a major financial burden on the health care system. Nationwide, these findings account for $300 million in readmission costs annually for colorectal surgery alone.

“Readmissions after surgery are common and they burden the health care system with exorbitant costs,” says Martin A. Makary, MD, MPH, an associate professor of surgery at the Johns Hopkins University School of Medicine and the senior author of a report on the new study published in the December issue of the journal Diseases of the Colon & Rectum. “While readmissions are sometimes unavoidable, many times they result from poor coordination of medical care. Everyone knows you can’t get readmissions down to zero but, at 23 percent, there’s a huge amount of room for improvement.

There is no reason we can’t cut that rate in half.” Says study leader Elizabeth Wick, MD, an assistant professor of surgery at Johns Hopkins: “Hospital readmissions are costly to the patient, costly to the system, delay recovery and victimize some patients multiple times.”

Using data from BlueCross BlueShield plans in eight states, Makary, Wick and their colleagues reviewed records of 10,882 patients who underwent colorectal surgery between 2002 and 2008. They found that 11.4 percent of patients were readmitted to the hospital within 30 days of discharge and another 12 percent were readmitted between days 31 and 90. Nearly 7 percent -- 725 patients -- were readmitted two or more times within the first three months after discharge.

Colorectal surgery patients are at high risk for readmission because of the location and complexity of their operations. Many suffer from a postsurgical infection or dehydration as the digestive system recovers from surgery. Stoma (ostomy) complications are also common. A stoma is sometimes needed to divert the intestinal tract outside the body.

Patients with a stoma are three times more likely to be readmitted within 30 days, and those with surgical-site infections are twice as likely, they found. Patients in the study needed colorectal surgery primarily because of cancer or diverticulitis, a chronic inflammation of the intestines. Nearly 19 percent of patients in the study contracted a surgical-site infection within 30 days of their operations.

Even a 5 percent reduction in surgical-site infections would have a significant impact on readmission rates and the associated costs, Wick says.

She notes that hospitals and surgeons are actively investigating ways to prevent surgical-site infections, and testing various interventions.

At The Johns Hopkins Hospital, for example, nurses are independently reviewing discharge plans before patients leave, making follow-up appointments for them and reviewing medication lists, tasks shown to prevent some return visits to the emergency department for minor concerns.

Makary says some hospitals are beginning to have nurses follow up with patients by phone in the days after discharge. Those deemed at high risk for readmission receive home visits from a nurse.

Both interventions are significantly less expensive than the cost of a new hospital stay.

He adds that many readmissions may be related to patients falling through the cracks. Sometimes they get lost in the process of setting follow-up appointments, don’t know what is considered to be a normal recovery, lack the right phone numbers to call for questions or are discharged with the wrong medications. He also suggests that some patients may be leaving the hospital too early and that “a little extra care on the front end” might stem costly readmissions.

The Centers for Medicare and Medicaid Services has targeted readmission rates after hospitalization for certain medical conditions as a factor in determining how much a hospital should be paid for treatment. Beginning in 2013, hospitals with higher than expected risk-adjusted 30-day readmission rates for patients with heart attacks, congestive heart failure and pneumonia will incur financial penalties. Public reporting of readmission rates is also planned, and health care experts anticipate that patients with other diagnoses, including those undergoing colorectal surgery, will be incorporated into this pay-for-performance measure in the future.

“Hospital readmissions are being used as a surrogate measure for determining quality of care,” Wick says. “If care isn’t as good, patients end up back in the hospital. We need to make sure patients don’t have to come back.”

Other Johns Hopkins researchers who worked on the study include Andrew D. Shore, PhD; Kenzo Hirose, MD; Andrew M. Ibrahim, B.A.; Susan L.Gearhart, MD; Jonathan Efron, MD; and Jonathan P. Weiner, DrPH

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More Intensive Chemotherapy Dramatically Improves Recurrence and Survival in Younger Patients with Aggressive Lymphoma

November 24 2011

Younger patients with diffuse large B-cell lymphoma given a more intensive regimen of chemotherapy combined with rituximab survive significantly longer, and are approximately twice as likely to remain in remission 3 years later, compared with patients given standard chemotherapy treatment plus rituximab, according to an article published Online First in The Lancet.

Over the past decade, combined treatment with the monoclonal antibody rituximab and a standard chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has substantially improved outcomes in lymphoma patients younger than 60 years. But some patients still relapse after a complete response to treatment, and the optimum chemotherapy regimen to combine with rituximab has yet to be established. Recent studies suggest that intensive chemotherapy (higher doses with shortened intervals between treatments) might benefit younger patients with aggressive lymphomas.

This study, conducted by the Groupe d’Etude des Lymphomes de I’Adulte (GELA), randomly assigned 379 patients aged 18–59 years with early intermediate-stage diffuse large B-cell lymphoma (one of the most common and aggressive forms of non-Hodgkin’s lymphoma) to receive either four cycles of dose-intensive chemotherapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) plus rituximab (R-ACVBP) at 2 week intervals, or eight cycles of the standard treatment (R-CHOP) at 3 week intervals. The dose-intensive regimen consists of two different phases—an induction phase of four cycles with higher doxorubicin and cyclophosphamide doses, given at a shortened interval, followed by a sequential consolidation treatment with drugs not used during induction.

After 3 years, event-free survival (patients not experiencing unplanned treatment for lymphoma, disease progression or recurrence, or death) was significantly better for patients in the dose-intensive group compared with those receiving standard treatment (81% vs 67%), with the more intensive chemotherapy reducing the risk of experiencing an event by 44%. Additionally, patients assigned to the intensified regimen had a 56% lower risk of death and were 52% less likely to experience disease progression compared with those given standard treatment.

But increasing the treatment intensity also significantly increased the likelihood of serious side effects. In particular, haematological and mucosal toxic effects were significantly more common in the dose-intense group, and a much higher proportion of patients experienced febrile neutropenia (38% vs 9%).

The authors say: “Intensified immunochemotherapy with R-ACVBP represents an alternative to R-CHOP to improve survival in patients younger than 60 years with diffuse large B-cell lymphoma of low-intermediate risk.”

They conclude by calling for further research to identify subsets of patients who are more likely to benefit from this intensive regimen.

In a comment, Julie Vose from Nebraska Medical Center, Omaha, USA, cautions: “This dose-intense regimen should only be used in patients in whom the expected relapse rate is sufficient to justify the higher toxic effects and cost profile.”

For full article and comment see: http://press.thelancet.com/lymphoma.pdf.

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FDA Commissioner Announces Avastin Decision

Drug not shown to be safe and effective in breast cancer patients

November 18 2011

FDA Commissioner Margaret A. Hamburg, MD, said today she is revoking the agency’s approval of the breast cancer indication for Avastin (bevacizumab) after concluding that the drug has not been shown to be safe and effective for that use.

Avastin will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme).

“This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use,” Dr. Hamburg said. “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”

Avastin’s risks include severe high blood pressure; bleeding and hemorrhaging; heart attack or heart failure; and the development of perforations in different parts of the body such as the nose, stomach, and intestines.

Today’s decision, outlined in Dr Hamburg’s 69-page opinion, involves Avastin used in combination with the cancer drug paclitaxel for those patients who have not been treated with chemotherapy for their form of metastatic breast cancer known as HER2 negative. This indication must now be removed from Avastin’s product labeling.

Dr. Hamburg’s decision is based on an extensive record, which includes thousands of pages submitted to a public docket, data from several clinical trials and the record from a two-day hearing held in June, 2011.

Avastin was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval. In this case, the accelerated approval was based on promising results from one study that suggested that the drug could provide a meaningful increase in the amount of time from when treatment is started until the tumor grows or the death of the patient.

After the accelerated approval of Avastin for breast cancer, the drug’s sponsor, Genentech, completed two additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone – not enough to outweigh the risk of taking the drug.

FDA’s Center for Drug Evaluation and Research, which is responsible for the approval of this drug, ultimately concluded that the results of these additional studies did not justify continued approval and notified Genentech it was proposing to withdraw approval of the indication.

Genentech did not agree with the Center’s evaluation of the data and, following the procedures set out in FDA regulations, requested a hearing on the Center’s withdrawal proposal, with a decision to be made by the Commissioner. That two-day hearing, which took place June 28-29, 2011, included recommendations from the FDA's Oncologic Drugs Advisory Committee (ODAC), voting 6-0 in favor of withdrawing approval of Avastin’s breast cancer indication. After the hearing, the public docket remained open until Aug. 4, 2011. (In an earlier meeting of the ODAC, that committee had voted 12-1 in favor of the removal of the breast cancer indication from the Avastin label).

“FDA is committed to working with sponsors to bring promising cancer drugs to market as quickly as possible using tools like accelerated approval,” Dr. Hamburg said. “I encourage Genentech to consider additional studies to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug.”

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FDA Approves Erwinaze to Treat a Form of Leukemia

November 18 2011

The U.S. Food and Drug Administration today approved Erwinaze (asparaginase Erwinia chrysanthemi) to treat patients with acute lymphoblastic leukemia (ALL), who have developed an allergy (hypersensitivity) to E. coli derived asparaginase and pegaspargase chemotherapy drugs used to treat ALL.

Acute lymphoblastic leukemia is a type of cancer in which the bone marrow makes too many lymphocytes, a type of white blood cell. White blood cells help the body fight infection and are formed in the bone marrow.

Erwinaze is injected directly into the muscle three times a week and works by breaking down one of the body’s protein building blocks (the amino acid, asparagine) that is present in the blood, and is necessary for the growth of all cells. Leukemia cells cannot produce this protein building block. When a patient is treated with Erwinaze the leukemia cells die. Normal human cells are able to make enough asparagine for their own needs through biosynthesis and will not be affected by treatment with Erwinaze.

“The approval of Erwinaze underscores the FDA’s commitment to the approval of drugs for conditions with limited patient populations with unmet medical needs using novel trial endpoints” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The safety and effectiveness of Erwinaze was evaluated in one clinical trial of 58 patients. Additional safety data was collected from the Erwinaze Master Treatment Protocol (EMTP), an expanded access program that enrolled 843 patients. Patients in both studies were unable to continue receiving pegaspargase or asparaginase derived from E. coli due to allergic reactions.

In the trial to support efficacy, the main outcome (endpoint) was the measurement of the proportion of patients with sustained asparaginase activity levels that correlate with better leukemia control and survival. All evaluable patients were shown to have maintained the pre-specified threshold for asparaginase activity at 48 or 72 hours after dosing.

Side effects associated with Erwinaze treatment include serious allergic reactions (anaphylaxis), inflammation of the pancreas (pancreatitis), high blood levels of liver enzymes (abnormal transaminases and bilirubin), blood clotting, bleeding (hemorrhage), nausea, vomiting and high blood sugar (hyperglycemia).

Prior to Erwinaze’s approval there were two asparagine specific enzyme products – Elspar (asparaginase injection) and Oncaspar (pegaspargase) – approved by FDA to treat patients with ALL. Both of these products are E. coli derived.

Erwinaze has been designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the U.S.

Erwinaze is manufactured by EUSA Pharma Inc. of Langhorne, Pa.

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Neurological and Executive Function Impairment Associated with Breast Cancer

November 14 2011

CHICAGO—Women who survive breast cancer show significant neurological impairment, and outcomes appear to be significantly poorer for those treated with chemotherapy, according to a report in the November issue of the Archives of Neurology, one of the JAMA/Archives journals. Breast cancer (BC) is one of the most common public health problems, with a worldwide estimated incidence of 39 per 100,000 individuals annually. Although primary BC has not been associated historically with neurological problems, a growing body of evidence suggests that patients are at increased risk for altered brain structure and function, according to background information in the article.

Shelli R. Kesler, PhD, and colleagues at Stanford University School of Medicine, Stanford, Calif., conducted an observational study to determine whether profiles of brain activation differ among BC survivors treated with or without chemotherapy, compared with healthy control women. The study included 25 women with BC who received chemotherapy, 19 women with BC who did not receive chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables. The women were asked to perform various tasks, and the researchers used functional MRI to measure activation in several areas of the brain. "Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls," the authors report. "The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other two groups," they write.

The study also found that the negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

"This study provides further evidence that primary BC may cause measurable brain injury," the authors conclude. "Women treated with chemotherapy may show additional prefrontal deficits and have difficulty compensating for neurobiological changes such that they also show impaired executive function." 

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Use of Low-Toxicity Conditioning Regimen Prior to Cell Transplantation Appears Promising For Older Adults with Blood, Bone Marrow Cancers

November 01 2011

CHICAGO—Older patients with advanced hematologic malignancies, such as leukemia and lymphoma, who received a conditioning regimen that included minimal-intensity radiation therapy prior to allogeneic (genetically different) hematopoietic cell transplantation (HCT; receipt of bone marrow or stem cells transplant) had survival and progression-free survival outcomes suggesting that this treatment approach may be a viable option for older patients with these malignancies, according to a study in the November 2 issue of JAMA.

"Increasing age has been historically implicated in higher mortality after high-dose allogeneic HCT for patients with hematologic malignancies [cancers of the blood or bone marrow]. Such transplants are preceded by intense, cytotoxic [toxic to cells] conditioning regimens aimed at reducing tumor burden. The risk of organ toxicities has limited the use of high-dose regimens to younger patients in good medical condition. Therefore, age cutoffs of 55 to 60 years have been in place for decades for high-dose HCT. This excluded the vast majority of patients from allogeneic HCT, given that median [midpoint] ages of patients at diagnoses of most hematologic malignancies range from 65 to 70 years," according to background information in the article.

To address this limitation, a nonmyeloablative (an approach using lower doses of chemotherapy and/or radiation that does not lead to eradication of all bone marrow cells prior to stem cell transplant) conditioning regimen for allogeneic HCT was developed. The regimen relies on graft-vs.-tumor effects to cure cancer and consists of the chemotherapy drug fludarabine and a low dose of total-body irradiation before HCT and a course of immunosuppression. "This regimen has allowed extension of allogeneic HCT to a previously unserved population of older or medically infirm patients," the authors write. Mohamed L. Sorror, MD, MSc, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues analyzed the outcomes of older patients with advanced hematologic malignancies who received minimally toxic nonmyeloablative allogeneic HCT. From 1998 to 2008, 372 patients ages 60 to 75 years (median age, 64 years) were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, before related (n = 184) or unrelated (n = 188) donor transplants. They also received postgrafting immunosuppression therapy. The primary outcomes measured for the study were overall and progression-free survival.

As of June 23, 2010, 133 of the 372 patients were alive, with a median follow-up of 55 months. Overall, disease progression or relapse has been the most common cause of death (n = 135). Nonrelapse deaths occurred among 104 patients, mainly due to infections, graft-vs.-host disease (GVHD), and multi-organ failure. Five-year rates of overall survival and progression-free survival were 35 percent and 32 percent, respectively. The overall 5-year cumulative incidence of relapse was 41 percent. Cumulative incidences for nonrelapse mortality at 5 years were comparable among the 3 age groups (27 percent for patients ages 60-64 vs. 26 percent for those ages 65-69 vs. 31 percent for those 70 or older). Five-year rates of overall survival were 38 percent for patients ages 60 through 64, 33 percent for those ages 65 through 69, and 25 percent for those 70 years or older. Also, comorbid conditions and risks for disease relapse, but not increasing age, were associated with worse outcomes. More than half of the older patients were never hospitalized, and two-thirds of survivors experienced eventual resolution of their chronic GVHD with return to normal or near-normal physical function.

"While there is much room for improvement, particularly with regard to relapse, these results are encouraging given the poor outcomes with nontransplantation treatments, especially for patients with high-risk acute myeloid leukemia, fludarabine-refractory chronic lymphocytic leukemia, or progressive lymphoma. The older population is increasing; demographic changes in the United States suggest that 20 percent of the population will be 65 years or older by 2030. Furthermore, increases of up to 77 percent in the number of newly diagnosed hematologic malignancies among the older population are expected to occur in the next 20 years. Greater age is also associated with increased medical comorbid conditions. Thus, establishing treatment options with curative outcomes and near-normal long-term physical function have become an important future goal for older patients with hematologic malignancies," the authors write.

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FDA Approves Erbitux to Treat Late-stage Head and Neck Cancer

November 07 2011

The U.S. Food and Drug Administration today approved Erbitux (cetuximab) for use with chemotherapy to treat patients with late-stage (metastatic) head and neck cancer.

Combined with chemotherapy, Erbitux extended the lives of those receiving the treatment combination compared with those receiving chemotherapy alone. Erbitux already is FDA-approved for certain types of colon cancer, and has been approved since 2006 for treatment of non-metastatic head and neck cancer in combination with radiation therapy (first-line) or as a single agent (following standard treatment).

According to the National Cancer Institute, head and neck cancers account for 3 percent to 5 percent of all cancers in the United States. These cancers typically develop in the nose, throat or mouth and they are more common in men and in people older than 50.

“Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multi-treatment approach for patients,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.” Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible.”

The safety and effectiveness of Erbitux for this indication is based on the results of a multi-center clinical study conducted outside the United States involving 442 patients with metastatic or recurrent head and neck cancer. The study used a non-U.S. approved version of cetuximab, rather than the U.S.-approved formulation.

Participants had inoperable or widespread disease and had not received prior chemotherapy. Half were selected to receive either the combination of cetuximab with chemotherapy (cisplatin or carboplatin and 5-fluorouracil) or chemotherapy (cisplatin or carboplatin and 5-fluorouracil) only. Patients receiving the cetuximab with chemotherapy combination lived, on average, 10.1 months compared with 7.4 months for those receiving chemotherapy only.

The most common side effects reported in patients receiving cetuximab were rash, itching (pruritus), nail changes, headache, diarrhea, and respiratory, skin, and mouth infections. Erbitux also can cause low serum magnesium, potassium, and calcium. Erbitux has been associated with serious and potentially life-threatening infusion reactions and heart attack. Patients taking Erbitux should limit their exposure to the sun.

Erbitux was first approved by the FDA in 2004 to treat Epidermal Growth Factor Receptor (EGFR)-positive late-stage colon cancer after patients stopped responding to chemotherapy. The treatment can be used alone or in combination with chemotherapy. Erbitux is co-marketed by New York City-based Bristol-Myers Squibb and Eli Lilly and Company based in Indianapolis, IN.

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Concurrent Chemo and Radiation Confers Survival Benefit in Nasopharyngeal Carcinoma Patients

November 04 2011

The combination of chemotherapy and radiation significantly improved the 5-year overall survival of patients with stage II nasopharyngeal carcinoma (NPC), according to a phase III study published November 4, 2011, in the Journal of the National Cancer Institute.

Nasopharyngeal carcinoma is endemic in Southern China and Southeast Asia, where radiotherapy (RT) has been the primary treatment. Although the National Comprehensive Cancer Network (NCCN) recommends concurrent chemo-radiotherapy (CCRT) for stage II disease, evidence regarding its efficacy is weak, and this has not been defined as a primary endpoint in phase III trials.

To determine whether or not combined chemotherapy and radiotherapy confers survival benefit to stage II NPC patients, Qui-Yan Chen, MD, PhD, of the Sun Yat-sen University Cancer Center in the People’s Republic of China, and colleagues, conducted a phase III trial of patients randomly assigned to receive either radiation therapy (114 patients) or combined chemotherapy and radiation (116 patients).

They also found that after a median follow-up of 60 months, 22.8% of patients in the radiation group had disease progression, compared to 11.2% in the concurrent therapy group. The researchers found that 5-year overall survival, progression-free survival, and distant metastasis-free survival were statistically significantly higher in the concurrent therapy group compared with the group receiving radiation alone.

The authors conclude that based on the results of this trial, which they believe to be the first phase III trial to compare CCRT and RT, the NCCN guidelines are reasonable. They hypothesize that early-stage disease may have a smaller distant tumor bulk, and thus CCRT may be more effective in eradicating distant micro-metastases. Although patients in the combined therapy group experienced more toxic side effects than patients who only received radiotherapy, the regimen was overall well tolerated when the chemotherapy drug dose was reduced. Chen et al write, “In summary, we think that the optimal choice for early-stage NPC is cisplatin, at a weekly dose of 30 mg/m², for both an optimal chemotherapy effect to eradicate small distant tumors and to ensure NPC patient compliance.” 

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ASCO Statement on White House Executive Order on Drug Shortages

October 31 2011

"The problem of cancer drug shortages continues to compromise the best possible patient care and is setting back the significant advancements being made in clinical cancer trials. ASCO has worked hard over the past year to raise awareness of these shortages and to find both immediate and permanent solutions. The White House executive order is a good first step to addressing the problem. ASCO stands ready to work with Congress and all oncology stakeholders on a comprehensive solution that puts patient health and research progress first," said ASCO President Michael Link, MD.

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We Can’t Wait: Obama Administration Takes Action to Reduce Prescription Drug Shortages, Fight Price Gouging

President Issues Executive Order, Backs Legislation to Require Drug Companies to Report Shortages

October 31 2011

President Obama today will sign an Executive Order directing the Food and Drug Administration (FDA) to take action to help further prevent and reduce prescription drug shortages, protect consumers and prevent price gouging. The President’s order directs FDA to broaden reporting of potential shortages of certain prescription drugs and to further expedite regulatory reviews that can help prevent or respond to shortages. Under the President’s order, FDA will also work with to the Department of Justice, which will examine whether potential shortages have led to illegal price gouging or stockpiling of life-saving medications.

In addition to signing the Executive Order, the White House announced the President’s support for bipartisan legislation (H.R. 2245 and S. 296) that will build on today’s actions to strengthen the FDA’s ability to prevent prescription drug shortages.

A small number of drugs in the U.S. experience a shortage in any given year, but the number of reported prescription drug shortages in the United States nearly tripled between 2005 and 2010. While FDA successfully prevented 137 drug shortages between January 1, 2010 and September 26, 2011, prescription drug shortages continue to threaten the health and safety of the American people.

These shortages could lead to price gouging, which has raised serious concerns. For example, the ranking member of the House Committee on Oversight and Government Reforms, when announcing his investigation into so-called gray markets, expressed concerns about a report that a leukemia drug whose typical contract price is about $12 per vial was being sold at $990 per vial – 80 times higher. A Premier healthcare alliance report released in August estimated that the typical gray market vendor marks up prices by an averaged 650 percent. At the extreme, a drug used to treat high blood pressure that was normally priced at $25.90 was being sold at $1,200 due to a drug shortage.

“The shortage of prescription drugs drives up costs, leaves consumers vulnerable to price gouging and threatens our health and safety,” said President Obama. “This is a problem we can’t wait to fix. That’s why today, I am directing my administration to take steps to protect consumers from drug shortages, and I’m committed to working with Congress and industry to keep tackling this problem going forward.”

Early notification of potential drug shortages can help prevent a shortage from becoming a crisis by allowing hospitals, doctors and manufacturers to take action to ensure medications remain available. Currently, the FDA can only require drug manufacturers to disclose the discontinuation of a critical drug when the drug is available through a single manufacturer. The President’s Executive Order directs the FDA to take additional steps to require drug manufacturers to provide adequate advance notice of manufacturing discontinuances or other actions that could lead to critical shortages. These additional steps to increase early notification will help achieve some of the goals of bipartisan legislation supported by the President that would require all prescription drug shortages to be disclosed to the FDA in advance and give the FDA new authority to enforce these requirements.

The Executive Order also requires FDA to expand its current efforts to expedite review of new manufacturing sites, drug suppliers, and manufacturing changes to help prevent shortages.

These actions are just some of the steps the Obama Administration is taking to ensure patients have access to the lifesaving medicines they need. Today, the Obama Administration also:

• Sent a letter to drug manufacturers reminding them of their responsibility to report the discontinuation of certain drugs to the FDA. The letter also encourages companies to voluntarily disclose to FDA potential prescription drug shortages in cases where disclosure is not currently required by law.
• Increased staffing resources for the FDA’s Drug Shortages Program to address the increased workload that will result from additional early notification of potential shortages by manufacturers.
• Released a report from the Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation (ASPE) that assesses the underlying factors that lead to drug shortages, and an FDA report on their role in monitoring, preventing, and responding to these shortages.

While the causes and many of the solutions are outside of the FDA’s authority, including the need for additional manufacturing capacity in the private sector, the Administration will continue its ongoing work with manufacturers and other stakeholders to help address drug shortages.

View a fact sheet to learn more about prescription drug shortages and the Obama Administration’s announcements.

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Antineoplastic Agents Associated With Thyroid Dysfunction

October 18 2011

Antineoplastic agents such as immunotherapies and targeted therapies that specifically target signaling pathways in cancer cells are associated with thyroid dysfunction in 20%-50% of cancer patients taking them, which can adversely affect patients’ quality of life, according to a study published October 18, 2011, in the Journal of the National Cancer Institute.

Over the past two decades, novel antineoplastic agents have been introduced that inhibit specific cellular processes to limit cancer cell growth.  Some of these agents cause thyroid dysfunction, which physicians often overlook because of the complexity of the clinical picture in cancer patients.  The symptoms of thyroid dysfunction, such as fatigue, weakness, depression, memory loss, and cardiovascular effects can be wrongly attributed to the primary disease. If under-diagnosed, thyroid dysfunction can adversely affect a patient’s quality of life.

To understand the thyroid-related side effects of antineoplastic agents, their frequency, and underlying mechanisms, Ole-Petter Riksfjord Hamnvik, MD, of the Division of Endocrinology, Diabetes, and Hypertension at Brigham and Women’s Hospital in Boston, and colleagues reviewed articles on thyroid dysfunction in cancer patients. The researchers found that there are no known strategies to prevent thyroid disease in patients receiving these new antineoplastic agents, and that possible preventative measures may be more toxic than the thyroid disease itself. They also say that screening for thyroid disease is likely beneficial, but note that there were no screening recommendations for asymptomatic patients in the literature they reviewed. However, in this review, the authors provide their own recommendations for patients based on the pattern of abnormalities with each agent, in addition to recommending the monitoring of thyroid function tests in clinical trials of antineoplastic agents.

The researchers also recommend several paths of research that should be pursued, namely knowledge of the biological effects of the antineoplastic agents on the thyroid, so they can identify possible preventative strategies and improve the proposed screening strategies. They also recommend performing large randomized clinical trials of screening and treatment of thyroid disease to evaluate the improvements in patient quality of life and fatigue as well as to evaluate the unanticipated effects of cancer outcomes. 

The researchers write, “Treatment for thyroid diseases is safe and likely to enhance patient quality of life, as well as potentially allow effective treatments for the underlying cancer to continue.”  They note however, that there are many levels of uncertainty and that most of the data are derived from case reports or case series, small prospective studies, or laboratory-based studies.  They recommend close monitoring of patients receiving these antineoplastic agents. “This may allow early recognition and treatment of thyroid disease, allowing continued treatment of the underlying cancer, as well as improving the quality of life of the patient.”

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Georgetown Researchers Examine 21-Year Series of Nipple Sparing Mastectomy Cases and Find No Cancers

October 27 2011

WASHINGTON, D.C. – A new study suggests some women needing a lumpectomy or mastectomy to treat their breast cancer have another potential option that is safe and effective, say researchers at Georgetown. They say the procedure known as a nipple sparing mastectomy is also a viable surgical option for women who choose to have their breasts removed because of their increased risk of developing the disease. For both groups of women, the surgery offers a chance for a more natural looking and normal feeling reconstructed breast as compared to other forms of mastectomy.

Nipple sparing mastectomy (NSM) involves the removal of the breast tissue while keeping intact the breast skin and nipple areola complex, which includes the nipple and darker pigmented circle of skin that surrounds it. The breast is usually reconstructed immediately.

A long standing concern with this type of surgery is that cancer cells might be left under the nipple, posing a threat over time. To examine the effectiveness of NSM, surgeons conducted a review of patient records for all women receiving the surgery at Georgetown University Hospital (GUH) between 1989 and 2010 including surgeries to either prevent or treat breast cancer. The results are published in the November issue of Plastic and Reconstructive Surgery, the official medical journal of the American Society of Plastic Surgeons.

“Our findings were reassuring. Of the 162 surgeries performed, we found no cancer recurrences and no new cancers in those receiving NSM,” says Scott Spear, MD, professor of plastic surgery at Georgetown University Medical Center and chairman of the department of plastic surgery at GUH. “The nipple-sparing technique is not appropriate for every patient depending upon their anatomy and type of breast pathology. Careful selection of the right patient for NSM is an important element of success.”

Some patients who received NSM at Georgetown had early-stage cancer or DCIS, which can become an invasive cancer if not treated properly. In fact, while the majority of women with early cancers typically have a lumpectomy, many women choose to have a mastectomy.

Georgetown breast cancer surgeon Shawna C. Willey, MD, says the first priority always is to treat or prevent the cancer. “We need to be able to offer women options that they know will successfully treat or prevent their cancer while at the same time, preserve their quality of life whether it be in their appearance or psychologically. Nipple sparing mastectomy goes a long way toward reaching that goal.” Willey is chief of breast cancer surgery at GUH, and she and Spear are members of the Georgetown Lombardi Comprehensive Cancer Center.

One step credited for why cancers didn’t develop later is that biopsies were done on the tissue that remained under the nipple area after the NSM. If abnormal cells in this tissue were identified, as it was in four cases reviewed, either the nipple or entire nipple areola complex later were removed.

A second concern for this kind of surgery is that the nipple areola complex (NAC) might not receive enough blood after the tissue and blood vessels below it are removed causing necrosis or tissue death. Researchers say the records showed three NACs became necrotic and required removal. Four other NACs had partial necrosis requiring surgery though the nipple and majority of the areola was spared.

“What we’ve learned from this review is that our established procedures and patient-selection protocol lead to favorable results,” confirms Spear. “As more data become available, I think we’ll see nipple sparing mastectomy play a larger role, particularly in the prevention setting.”

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Study Suggests That a 2cm Excision Margin for Melanomas Thicker Than 2mm is Safe and Sufficient

October 23 2011

Controversy surrounds what is the most appropriate surgical excision margin for skin melanomas thicker than 2mm. A trial published Online First by The Lancet suggests that a 2cm excision margin for such melanomas is safe and sufficient, since it results in similar levels of recurrence as a larger margin of 4cm. The article is by Dr Peter Gillgren, Karolinska Institutet and Stockholm Söder Hospital, Stockholm, Sweden, and colleagues.

The incidence of skin melanoma is increasing in Scandinavia and other countries with predominantly white populations. In Sweden the average increase is around 4% per year for both men and women.  Furthermore, the average age of patients diagnosed with a skin melanoma is low compared with other cancers. When operating to remove melanomas, a balance must be struck.  There may be relapse-risk with a narrow excision, which could compromise disease-free survival or, worse, overall survival. However, the authors highlight that with a surgical margin of 2 cm, the skin can be closed without skin grafting or skin flaps in most cases. On the other hand, wide excisions might also lead to bad cosmetic results, lymphatic obstruction, long hospital stay, frequent need for skin grafts, or complicated skin flap reconstructions. Current recommendations vary between countries with 2cm and 3cm excision margins commonly recommended.

The authors carried out their randomised controlled trial in nine European centres across Sweden, Norway, Denmark, and Estonia. Patients with skin melanoma thicker than 2 mm, at clinical stage IIA–C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. The primary endpoint was overall survival. A total of 465 patients were allocated to 2-cm resection, and 471 to receive 4-cm resection. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of around 7 years, similar numbers of patients in each group had died: 181 (39%) patients in the 2-cm group and 177 (38%) in the 4-cm group. 5-year overall survival was the same in both groups at 65%. Any 5-year-recurrence was also the same at 44% in both groups (or put another way, the proportion of relapse-free patients at 5 years was 56% in both groups).

They conclude: “Our large study shows that melanoma patients with a tumour thicker than 2 mm can be safely treated with a 2-cm margin without any effect on overall survival and recurrence…meta-analysis should be done of all randomised trials of cutaneous melanoma thicker than 2 mm.”

In a linked comment, Professor John F Thompson, Melanoma Institute Australia, North Sydney, NSW, Australia, and Dr David W Ollila, Division of Surgical Oncology and Endocrine surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA, say: “The next question to be addressed is whether a 2-cm margin is preferable to a 1-cm margin or whether a 1-cm margin is sufficient and safe. Morbidity and healthcare costs could be decreased if a 1-cm margin is equivalent or non-inferior to a 2-cm margin. A proposal for such a large scale, multicentre trial is being developed.”

For full article and comment see: http://press.thelancet.com/melanoma.pdf

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More Surgery in Early-Stage Laryngeal Cancer Treatment

More Chemoradiation for Advanced-Stage Patients

October 17 2011

CHICAGO – The use of surgery to treat early-stage laryngeal cancer (cancer of the voice box) is increasing in the United States, and chemotherapy in combination with radiation therapy is being used increasingly to treat patients in an advanced stage of the disease, according to a report in the October issue of Archives of Otolaryngology – Head & Neck Surgery, one of the JAMA/Archives journals.

  Cancer of the larynx, or voice box, was diagnosed in nearly 13,000 people in the U.S. in 2010, and 3,660 were projected to die from the disease, according to background information in the article. Early-stage laryngeal cancer has traditionally been treated with radiation therapy or surgical resection (removal of part of the larynx) with comparable successful outcomes.

  Amy Y. Chen, MD, MPH, and colleagues at Emory University and the American Cancer Society, Atlanta, conducted a study to examine trends and four-year survival rates of surgical and non-surgical treatment for laryngeal cancer. They analyzed data on 131,694 laryngeal cancer cases diagnosed from 1985 to 2007, identified from the National Cancer Database. The primary treatment information included radiation therapy (RT), chemoradiation (CRT, chemotherapy in combination with radiation therapy), and curative intent surgery.

  The authors found that surgical resection of early-stage laryngeal cancer increased over the years, with a corresponding decrease in radiation.

  “Among patients with early-stage cancer, the proportion receiving primary surgery increased (from 20 percent in 1985 to 33 percent in 2007), whereas the use of RT decreased from 64 percent to 52 percent,” they report. “The four-year survival rate for patients with early-stage laryngeal cancer treated with surgery was higher than the rate for those treated with RT (79 percent vs. 71 percent).”

  “Among patients with advanced-stage cancer, the use of CRT increased from less than 7 percent to 45 percent, whereas the use of total laryngectomy [surgical removal of the voice box] decreased from 42 percent to 32 percent,” they continue.

  Advanced-stage patients who had total laryngectomy had a four-year survival rate of 51 percent. The survival rate for patients treated with CRT was 48 percent, and for those treated with RT the survival rate was 38 percent.

  Patients who lived in areas with higher socioeconomic status zip codes and who had private insurance were more likely to be treated with surgery for early-stage laryngeal cancer, and to receive CRT for advanced-stage cancer. Early-stage patients who were not African American, and who were treated at academic facilities, were more likely to receive surgery. Younger patients with advanced-stage cancer were more likely to be treated with CRT.

  “Not only were clinical factors associated with type of treatment, but select sociodemographic elements were also associated with treatment,” the authors conclude. “Further investigation as to the decision-making process of patients with different sociodemographic backgrounds will assist in mitigating the differences in survival for this group of patients.”

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ASCO Issues Updated Guideline on the Use of Antiemetic Agents to Prevent Vomiting and Nausea after Chemotherapy and Radiation

September 26 2011

ALEXANDRIA, VA - The American Society of Clinical Oncology (ASCO) today issued an update to its clinical practice guideline on the use of antiemetic medications to prevent vomiting and nausea resulting from treatment with chemotherapy and/or radiation. The new guideline includes comprehensive, stratified recommendations on the use of antiemetics during treatment with chemotherapy drugs that are classified as high, moderate, minimal and low risk for causing vomiting and nausea.

The updated guideline, American Society of Clinical Oncology Clinical Practice Guideline Update on Antiemetics, was published online today in the Journal of Clinical Oncology. The guideline was originally published in 1999 and previously updated in 2006. The new recommendations were developed by ASCO's Antiemetics Guideline Panel and are based on a systematic review of new and existing medical literature.

More than half of all cancer patients experience nausea or vomiting during the course of their treatment. If nausea or vomiting becomes severe enough, patients can experience dehydration and other health problems. In some cases these side effects can cause cancer treatments to be delayed, halted or changed, which may have a detrimental effect on overall treatment outcomes. Importantly, in the past two decades, newer approaches and better antiemetic medications have reduced the incidence of both nausea and vomiting in cancer patients undergoing therapy.

"Antiemetics serve a vital role in reducing the risk of nausea and vomiting in cancer care, and when used appropriately, can vastly improve patients' treatment experience and enable them to carry on with their lives," said panel co-chair and first author Ethan Basch, MD, associate attending physician at Memorial Sloan-Kettering Cancer Center in New York "Over the past two decades, major strides have been made in recognizing the scope of this problem. There have been improvements in stratifying the risk of side effect risks according to the type of drug treatment used. This guideline update reflects further progress refining antiemetic approaches and minimizing these side effects."

The guideline provides detailed information about the risk of vomiting and nausea associated with various anti-cancer agents and radiation therapy, as well as the specific recommended antiemetic regimens for each. Basch points out that a major goal in cancer care is to personalize therapy to each patient, and that this guideline helps physicians do so by stratifying patients' antiemetics needs based on their particular treatments.

One key recommendation in this update is the reclassification of the risk for vomiting and nausea from the combination of an anthracycline and cyclophosphamide, a commonly used chemotherapy regimen. Each drug alone is classified as having a moderate risk, but based on continued scientific data, the combination now is considered high-risk. This chemotherapy combination is widely used in patients with breast cancer and non-Hodgkin's lymphoma. This change is significant because of the widespread use of this combination, and the potential to improve the patient's experience during treatment and avoid treatment delays or dose reductions.

In addition, the guideline provides direction on the use of fosaprepitant, a relatively new intravenous formulation of aprepitant. Data suggest that fosaprepitant is equivalent to aprepitant, in terms of control and prevention of nausea and vomiting. However, fosaprepitant is given for one day, while aprepitant is given for three days to patients undergoing chemotherapy that present a high risk of vomiting and nausea. This may represent a more convenient or feasible option for some patients. These drugs are part of the guideline-recommended three-drug combination (which includes a 5-HT3 receptor antagonist and the corticosteroid dexamethasone) for all patients who receive high-risk chemotherapy.

"In general, we have more effective and better tolerated antiemetic agents today, and we have also learned how to use the available agents in more effective ways," said panel co-chair Gary Lyman, MD, MPH, professor of medicine at Duke University and the Duke Cancer Institute in Durham, NC. "Overall, oncologists have a better understanding and an increasing number of tools to reduce the side effects of cancer treatment. In addition to better strategies for preventing vomiting, we've made tremendous progress in preventing infection and managing pain, as well as addressing the psychological and emotional challenges of cancer."

Specifically, some of the guideline's other recommendations included:

• For patients who receive chemotherapy with a moderate risk of causing nausea and vomiting, the two-drug combination of palonosetron and dexamethasone is recommended. If palonosetron is unavailable, a first generation 5-HT3 serotonin antagonist may be substituted.
• For chemotherapy agents that carry a low risk of inducing vomiting or nausea, the panel recommended a single dose of dexamethasone prior to chemotherapy. It recommended that no antiemetic agent be routinely given before or after chemotherapy to prevent nausea and/or vomiting brought on by minimal-risk chemotherapy drugs.
• For patients who receive high-risk radiation therapy, the panel recommended that patients receive a 5-HT3 antagonist before each radiation fraction, and at least 24 hours after completing radiation therapy. Patients should also be given a five-day course of dexamethasone during fractions one to five.

To view a full copy of the guideline click here.

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AUA Responds to New Recommendations on Prostate Cancer Screening

Association urges men to speak with their physicians about the value of prostate cancer testing

October 07 2011

LINTHICUM, MD – The American Urological Association (AUA) today released the following statement in response to the U.S. Preventive Services Task Force draft recommendations on the use of the prostate-specific antigen (PSA) test. The statement is attributed to AUA President Sushil S. Lacy, MD:

The American Urological Association (AUA) applauds the U.S. Preventive Services Task Force for its interest in reviewing the use of the prostate-specific antigen (PSA) test. However, we are concerned that the Task Force’s recommendations will ultimately do more harm than good to the many men at risk for prostate cancer both here in the United States and around the world. The AUA’s current clinical recommendations support the use of the PSA test, and it is our feeling that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging or risk assessment and monitoring of prostate cancer patients.

Not all prostate cancers require active treatment and not all prostate cancers are life threatening. The decision to proceed to active treatment is one that men should discuss in detail with their urologists to determine whether active treatment is necessary, or whether surveillance may be an option for their prostate cancer.

The AUA is currently preparing a new clinical guideline on this topic, and has convened a panel of experts to review not only the use of the PSA test, but also early detection of prostate cancer overall, taking into account the new tests and diagnostics that are becoming available. Until there is a better widespread test for this potentially devastating disease, the USPSTF – by disparaging the test – is doing a great disservice to the men worldwide who may benefit from the PSA test.

For more information about the AUA’s position on the early detection of prostate cancer, or to arrange an interview with an expert urologist, please contact the AUA Communications Office at 410-689-3932.

About the American Urological Association: Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is the pre-eminent professional organization for urologists, with more than 18,000 members throughout the world. An educational nonprofit organization, the AUA pursues its mission of fostering the highest standards of urologic care by carrying out a wide variety of programs for members and their patients.

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Ovarian Cancer Patients Survive Longer with BRCA2 Mutated in Tumors

DNA-damaging platinum drugs work better against them; BRCA1 variations have no effect

October 11 2011

HOUSTON — Women with high-grade ovarian cancer live longer and respond better to platinum-based chemotherapy when their tumors have BRCA2 genetic mutations, researchers at The University of Texas MD Anderson Cancer Center and the Institute for Systems Biology report in the Oct. 12 issue of the Journal of the American Medical Association.

"BRCA2-mutated tumors are more vulnerable to these DNA-damaging agents, which is really exciting because there are a number of drugs in clinical trials now that block DNA repair that might prove effective against these tumors in combinations," said senior author Wei Zhang, PhD, professor in MD Anderson's Department of Pathology.

BRCA2 and its cousin, BRCA1, are tumor-suppressing genes involved in DNA repair that, when mutated, raise a woman's risk for having breast or ovarian cancer.

"Uncovering the separate potential effects of BRCA1 and BRCA2 mutations takes us a step towards a more personalized approach to treating ovarian cancer, and perhaps other cancers," Zhang said. "This paper suggests those two genes, and the many others involved in DNA repair, are prime targets for further research."

Past studies of the possible clinical impact of BRCA1 and BRCA2 mutations tended to look at the two genes together and were limited by small sample sizes.

First author Da Yang, PhD, an Odyssey Fellow in MD Anderson's Department of Pathology, said their in-depth study was made possible by The Cancer Genome Atlas project. TCGA published a study of 489 cases of  high-grade serous ovarian cancer, the most common form of the disease,  that combined an exhaustive analysis of each tumor's genome with comprehensive clinical data on each patient.

"TCGA gave us enough analytical power to differentiate between BRCA1 and BRCA2 mutations and conduct a survival analysis," Yang said.

Improved overall survival
Of 316 cases, 29 tumors had BRCA2 mutations tumors and 37 had BRCA1 mutations. Tumors were similar in grade and stage.  Findings include:

• 61 percent of patients with BRCA2 mutations survived for five years, compared with 25 percent of those with normal BRCA2 in their tumors.
•  percent of those with BRCA2 mutations lived three years after surgery and platinum treatment without disease progression, compared with 16 percent of those with normal BRCA2.
• BRCA1 mutations in tumors were not associated with survival.
• All of those with BRCA2 mutations responded to platinum chemotherapy, compared to 82 percent with the normal gene and 80 percent whose tumors had BRCA1 mutations.
• Their response to chemotherapy lasted 18 months, compared with 11.7 months for normal BRCA2 and 12.5 months for BRCA1 mutations.
• Tumors with BRCA2 variations also are hypermutants - they had more genetic mutations - with 84 mutations per tumor sample compared to 52 for normal BRCA2.

Zhang said this last aspect - called the hypermutator phenotype - might be both a factor in the development and growth of the tumor and a sign of its vulnerability.

BRCA2 is normally involved in the repair of double-strand DNA breaks. Cells with BRCA2 mutants are less capable of repair, allowing other genetic mutations to survive and grow, the type of genomic instability that cancer thrives upon.

However, cancer cells in turn rely on DNA repair to defend themselves against DNA-damaging drugs, such as platinum-based agents. So adding drugs that inhibit DNA repair could increase the effectiveness of chemotherapy, Zhang noted. PARP-inhibitors, a new class of drug in clinical trials, block DNA repair and may also be effective in treating BRCA2 mutated ovarian cancer.

Additional studies of the function of BRCA1 and BRCA2 mutations are needed to more fully understand and exploit their findings to treat cancer, Zhang and colleagues note.

The Cancer Genome Atlas is a joint project of the National Cancer Institute and the National Human Genome Research Institute, both of the National Institutes of Health, to comprehensively characterize changes in genetic mutation and regulation of various cancers. 

Co-authors with Zhang and Yang are Sofia Kahn, PhD, and Yan Sun, MD, PhD, of MD Anderson's Department of Pathology; Kenneth Hess, PhD, of MD Anderson's Department of Biostatistics, Anil Sood, MD, of MD Anderson Departments of Cancer Biology and Gynecologic Oncology and Reproductive Medicine and the Center for RNAi and Non-Coding RNA; and Ilya Shmulevich, PhD, Institute for Systems Biology in Seattle. 

This research was funded by the National Cancer Institute; the Blanton-Davis Ovarian Cancer Research Program, MD Anderson's NCI Specialized Program in Research Excellence in Ovarian Cancer; MD Anderson's Odyssey Fellows Program; and an ASLA-Fulbright Research Grant.

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Drug Prevents Bone Loss Side Effects of Breast Cancer Medication

October 10 2011

A new study has found that an osteoporosis drug protects against the bone damaging side effects of certain breast cancer medications. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that some breast cancer patients could take zoledronic acid in addition to their anti-cancer medications to maintain bone health.

Drugs called aromatase inhibitors stop the production of estrogen in postmenopausal women and therefore make less estrogen available to stimulate the growth of certain breast cancer cells. Many postmenopausal women with breast cancer are routinely treated for several years with these potentially life-saving drugs, but the agents can cause bone loss and fractures.

Adam Brufsky, MD, PhD, of the University of Pittsburgh Cancer Institute, and his colleagues conducted a study to see if the bone drug zoledronic acid could prevent and treat bone loss in postmenopausal breast cancer patients. In their five-year study, called Z-FAST, 602 postmenopausal women with early breast cancer who were receiving the aromatase inhibitor letrozole were randomized to receive zoledronic acid simultaneously with letrozole or only after bone loss or fractures occurred.

The investigators observed significant and progressive increases in bone density throughout the five years of the study in women who initiated zoledronic acid at the start; in contrast, significant decreases in bone density occurred when zoledronic acid administration was delayed until bone loss was apparent. Over time, though, the rate of bone density decline in the delayed group slowed, most likely because more delayed patients received zoledronic acid by the end of the study. These findings indicate that bone density is maintained more effectively with upfront zoledronic acid, but bone loss is likely reversible so that initiating zoledronic acid, even after bone loss has developed, is beneficial.

“This study shows that bone loss from aromatase inhibitors can be prevented long term with a safe and effective drug that prevents osteoporosis,” said Dr. Brufsky. Zoledronic acid is currently approved by the U.S. Food and Drug Administration for conditions including osteoporosis and bone complications of cancer.

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Seattle Researchers Map Genome of Advanced, Lethal Prostate Cancers and Discover 'Hypermutations'

First comprehensive assessment of DNA errors that drive advanced prostate cancer

September 26 2011

SEATTLE — A team of researchers at Fred Hutchinson Cancer Research Center and the University of Washington has conducted the first comprehensive assessment of every gene in the genome of advanced, lethal prostate cancer. Until now, the genetic composition of such tumors had been poorly defined.

In the process, they have discovered a number of potential key drivers – recurrent genetic mistakes – common to advanced prostate cancer that may contribute to disease progression. The researchers also have identified several instances of genetic “hypermutation,” a gross excess of single-letter DNA “spelling errors” that could cause the cancer to become resistant to therapies commonly used to slow the progression of advanced prostate cancer, such as androgen-blocking drugs and surgical castration.

Corresponding authors Peter S. Nelson, MD, a member of the Hutchinson Center’s Human Biology Division, and Jay Shendure, MD, PhD, an associate professor of Genome Sciences at UW and an affiliate member of the Hutchinson Center’s Human Biology Division, and colleagues report their findings September 26, 2011, in the Proceedings of the National Academy of Sciences Early Edition. The lead author of the paper was Akash Kumar, a graduate student in Genome Sciences and an MD-PhD candidate at UW.

“The most interesting finding to come out of our DNA sequencing project was the discovery of three aggressive tumor types that had 10 times the number of mutations compared to the other advanced prostate cancers we studied,” Nelson said. “That was very surprising and unusual. We don’t know the cause of these hypermutated tumors, but the frequency of the mutations suggests these tumors might evolve very rapidly to develop resistance to therapies.”

The discovery of these genetic mutations should provide clues that illuminate why some prostate cancers are lethal, and potentially could be used to develop screening tests for early detection or drug targets to slow or halt cancer growth, Nelson said.

“The mutations underlying the progression of prostate cancer to an advanced state have been understudied to date,” Shendure said. “Although further work is certainly necessary, our hope is that identifying the genes in which these mutations occur will facilitate biological insights and the development of new therapeutic strategies.”

For the study, the researchers determined the mutational status of 23 aggressive and lethal, drug-resistant human prostate cancers, including those that had metastasized, or spread, beyond their primary site of origin and those that had not. They used a technology called exome sequencing to survey the mutational landscape. This method is more efficient and cost-effective than whole-genome sequencing because it zeroes in on just 1 percent of the human genome – the exome – a highly functional region that harbors the majority of disease-causing mutations.

In aggressive tumors, the researchers identified a number of genes with recurrent germline (inheritable) or somatic (noninheritable) mutations, including variants in TP53, a gene that encodes tumor protein p53, which normally functions as a tumor suppressor; and GPC6, a gene that encodes glypican-6, which regulates cell growth and division. They also found recurrent mutations in several genes whose mechanisms in prostate cancer development are not yet well understood, as well as thousands of individual, or “personal,” mutations unique to individual tumors.

The researchers also found that of nearly 90 mutations associated with tumors that are resistant to testosterone suppression – a common treatment for advanced prostate cancer – each tumor studied had at least one mutation in the Wnt signaling pathway, a network of proteins known to play a variety of important roles in embryonic development and cancer, among other things.

Nelson and researchers at the Hutchinson Center contributed to the concepts underlying the study and confirmed the identified mutations using alternate technologies. Shendure and colleagues at the UW provided key tissue samples and a majority of the exome sequencing and analysis, among other contributions.

Funding for the research came from the U.S. Department of Defense, National Institutes of Health, Richard M. Lucas Foundation, Prostate Cancer Foundation and Pacific Northwest Prostate Cancer Specialized Programs of Research Excellence.

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Couples Counseling Helps Improve the Sex Lives of Prostate Cancer Survivors and their Spouses

September 26 2011

Both internet-based counseling programs and face-to-face therapy sessions for couples improve the sex lives of prostate cancer survivors and their spouses. That is the finding of a new study published early online in Cancer, a peer-reviewed journal of the American Cancer Society. The results suggest that couples counseling can provide additional benefits to patients’ sex lives beyond those experienced from medications such as erectile dysfunction pills.

Despite efforts to make therapies for prostate cancer less destructive to men’s sex lives, most men who are treated end up with erection problems. Many also lose some desire for sex and have a diminished ability to reach or enjoy orgasms.

Leslie Schover, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues tested the effectiveness of different strategies to improve the sex lives of prostate cancer survivors and their spouses. Their study included 115 couples in which the man’s prostate cancer treatment had taken place a little less than two years previously. At the start of the study, half of the couples waited three months for an intervention while the other half either went through three face-to-face sex therapy sessions or interacted with a Web site that presented the same information with email feedback from a counselor. A third group of 71 couples who lived too far away for face-to-face therapy also received internet-based therapy.

After three months, no benefits were seen among couples in the waiting group, and they were then assigned to one of the two treatments. Both partners were asked to complete questionnaires that assessed sexual function and satisfaction before starting counseling, after the treatment, and at 6-month and 1-year follow-up.

Both face-to-face therapy and internet-based therapy were effective at improving men’s sexual function and satisfaction, based on scores from questionnaires. Also, when the man’s score improved, the woman’s did as well. Even one year after the end of the counseling period, couples were still better off than before the program began. For those couples in the internet-based version, however, only those who completed most of the Web program improved significantly.

Dr. Schover noted that while both types of interventions improved couples’ sex lives, an internet-based program may be easier to implement than one that is conducted face-to-face. “An internet-based treatment has the advantage of costing less in counselor time and allowing expert health care providers to help cancer survivors who live too far away from a city or cancer center,” she said.

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Uninsured Breast Cancer Patients Not Informed of Reconstructive Options

Patient Education Significantly Increases Breast Reconstruction Rates, Study Finds

September 22 2011

DENVER - More than half of uninsured women with breast cancer never receive adequate information regarding their reconstructive options after mastectomy, says a study being presented at the American Society of Plastic Surgeons (ASPS) annual conference, Plastic Surgery 11 THE Meeting, September 23-27, 2011, in Denver. However, pre-operative patient education significantly increases the rate of breast reconstruction in uninsured patients, the study finds.

"Despite the clearly documented benefits of breast reconstruction after mastectomy, there has been an enormous disparity between rates of reconstruction for insured and uninsured American women," said Jamie Levine, MD, ASPS Member Surgeon and study co-author. "Private and government insurance are required to cover breast reconstruction for cancer patients. In spite of this, our research shows that many uninsured patients are being denied a key conversation about breast reconstruction that should take place at the time of diagnosis."

The study examined 54 uninsured women diagnosed with breast cancer at a public hospital. Fifty-two percent of patients had no knowledge about breast reconstruction options prior to receiving patient education. However, patient education (multi-media and other tools, referral to a plastic surgeon for consultation) significantly increased the percentage of uninsured women who had breast reconstruction (76% vs. 47%), most notably among Blacks (100% vs. 63%) and Asians (73% vs. 34%). Nationally, breast reconstruction rates among the uninsured have been reported as low as eight percent, the authors note.

"When uninsured patients were given the opportunity to understand what options were available to them, they chose reconstruction," said Dr. Levine. "These patients deserve the same right, as those insured, to make informed decisions about their bodies and healthcare. Patient education builds the kind of equality in patient care physicians strive for."

Dr. Levine emphasizes the importance of initiating patient education at the point of initial diagnosis. "Ensuring cancer patients are receiving information about all their treatment options must become a multidisciplinary commitment. By offering breast reconstruction at the point of diagnosis we can build hope, empower women, and provide better outcomes."

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A Ray of Hope for Some Lung Cancer Patients

September 12 2011

A new treatment standard may be in the making for some patients with lung cancer, a study headed by Winship Cancer Institute’s executive director suggests.

More patients with non-small cell lung cancer (NSCLC) that is locally advanced lived five years or longer when they had received radiation and chemotherapy at the same time (concurrently) than those who had received the treatment in sequence, the study found.

Traditional treatment protocols typically call for chemotherapy to be administered first for patients with locally advanced NSCLC. Patients then undergo radiation therapy.

In this study, however, more patients who received the therapies concurrently – during the same general time period -- were still living after five years than those who received the therapies in sequence. The study was published online in the Sept. 8 2011 Journal of the National Cancer Institute.

Walter J. Curran, Jr., MD, principal investigator of the study and executive director of Winship Cancer Institute, said the findings suggest a new treatment standard for this group of patients.

“The significant increase in five-year survival for patients receiving concurrent versus sequential treatment establishes a new treatment standard for this large population of lung cancer patients,” said Curran, who is also chair of the Radiation Therapy Oncology Group, which conducted the clinical trial. RTOG is a National Cancer Institute-supported group of cancer research centers that cooperatively conduct clinical trials.

The Phase III study enrolled 610 participants with stage III, NSCLC at 153 institutions across North America. Stage III, NSCLC is locally advanced disease that has not spread to other organs. Many who are diagnosed with the disease were never smokers. The study participants were randomized into three arms. One arm received cisplatin-based chemotherapy and radiation therapy in sequence – that is, chemotherapy first, then radiation therapy. Another arm received radiation and chemotherapy concurrently once daily. The third arm received the therapies concurrently but twice daily.

The patients in the arm who received concurrent therapy once daily fared the best of the three arms. Of those patients, 16 percent were still living after five years. Those who received the therapies sequentially fared least well; 10 percent were still living after five years. Those who received concurrent therapy twice daily fared better than those who received the therapies sequentially, but not as well as those who received concurrent therapy once a day. Of those, 13 percent were still living after five years.

The news is important because lung cancer remains the nation’s number one cancer killer. Lung cancer is difficult to treat, in large part because it often is diagnosed in late stages. About 50,000 Americans are diagnosed each year with stage III NSCLC. This study advances the knowledge about how best to treat those patients. It also suggests new treatment strategies for further study. For example, RTOG is now evaluating the addition of another drug, cetuximab, to the regimen for patients with stage III, NSCLC.

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Purdue Technology Used in First Fluorescence-guided Ovarian Cancer Surgery

September 18 2011

West Lafayette, IN - The first fluorescence-guided surgery on an ovarian cancer patient was performed using a cancer cell "homing device" and imaging agent created by a Purdue University researcher.

The surgery was one of 10 performed as part of the first phase of a clinical trial to evaluate a new technology to aid surgeons in the removal of malignant tissue from ovarian cancer patients. The method illuminates cancer cells to help surgeons identify and remove smaller tumors that could otherwise be missed.

Philip Low, the Ralph C. Corely Distinguished Professor of Chemistry who invented the technology, said surgeons were able to see clusters of cancer cells as small as one-tenth of a millimeter, as opposed to the earlier average minimal cluster size of 3 millimeters in diameter based on current methods of visual and tactile detection.

"Ovarian cancer is notoriously difficult to see, and this technique allowed surgeons to spot a tumor 30 times smaller than the smallest they could detect using standard techniques," said Low, who also is a member of the Purdue University Center for Cancer Research. "By dramatically improving the detection of the cancer - by literally lighting it up - cancer removal is dramatically improved."

The technique attaches a fluorescent imaging agent to a modified form of the vitamin folic acid, which acts as a "homing device" to seek out and attach to ovarian cancer cells. Patients are injected with the combination two hours prior to surgery and a special camera system, called a multispectral fluorescence camera, then illuminates the cancer cells and displays their location on a flat-screen monitor next to the patient during surgery.

The surgeons involved in this study reported finding an average of 34 tumor deposits using this technique, compared with an average of seven tumor deposits using visual and tactile observations alone. A paper detailing the study was published online Sunday (Sept. 18) in Nature Medicine.

Gooitzen van Dam, a professor and surgeon at the University of Groningen in The Netherlands where the surgeries took place, said the imaging system fits in well with current surgical practice.

"This system is very easy to use and fits seamlessly in the way surgeons do open and laparoscopic surgery, which is the direction most surgeries are headed in the future," said van Dam, who is a surgeon in the division of surgical oncology and Bio-Optical Imaging Center at the University of Groningen. "I think this technology will revolutionize surgical vision. I foresee it becoming a new standard in cancer surgery in a very short time."

Research has shown that the less cancerous tissue that remains, the easier it is for chemotherapy or immunotherapy to work, Low said.

"With ovarian cancer it is clear that the more cancer you can remove, the better the prognosis for the patient," he said. "This is why we chose to begin with ovarian cancer. It seemed like the best place to start to make a difference in people's lives."

By focusing on removal of malignant tissue as opposed to evaluating patient outcome, Low dramatically reduced the amount of time the clinical trial would take to complete.

"What we are really after is a better outcome for patients, but if we had instead designed the clinical trial to evaluate the impact of fluorescence-guided surgery on life expectancy, we would have had to follow patients for years and years," he said. "By instead evaluating if we can identify and remove more malignant tissue with the aid of fluorescence imaging, we are able to quantify the impact of this novel approach within two hours after surgery. We hope this will allow the technology to be approved for general use in a much shorter time."

Low and his team are now making arrangements to work with the Mayo Clinic for the next phase of clinical trials.

The technology is based on Low's discovery that folic acid, or folate, can be used like a Trojan horse to sneak an imaging agent or drug into a cancer cell. Most ovarian cancer cells require large amounts of the vitamin to grow and divide, and special receptors on the cell's surface grab the vitamin - and whatever is linked to it - and pull it inside. Not all cancer cells express the folate receptor, and a simple test is necessary to determine if a specific patient's cancer expresses the receptor in large enough quantities for the technique to work, he said.

Ovarian cancer has one of the highest rates of folate receptor expression at about 85 percent. Approximately 80 percent of endometrial, lung and kidney cancers, and 50 percent of breast and colon cancers also express the receptor, he said.

Low also is investigating targeting molecules that could be used to carry attached imaging agents or drugs to forms of cancer that do not have folate receptors.

He next plans to develop a red fluorescent imaging agent that can be seen through the skin and deep into the body. The current agent uses a green dye that had already been through the approval process to be used in patients, but cannot easily be seen when present deep in tissue. Green light uses a relatively short wavelength that limits its ability to pass through the body, whereas the longer wavelengths of a red fluorescent dye can easily be seen through tissue.

"We want to be able to see deeper into the tissue, beyond the surface," Low said. "Different cancers have tumors with different characteristics, and some branch and wind their way deeper into tissue. We will continue to evolve this technology and make improvements that help cancer patients."

In addition to Low and van Dam, the paper's authors include George Themelis, Athanasios Sarantopoulos and Vasilis Ntziachristos of the Institute for Biological and Medical Imaging at the Technical University of Munich in Germany; Lucia Crane, Niels Harlaar, Rick Pleijhuis, Wendy Kelder and Johannes de Jong of the division of surgical oncology of the BioOptical Imaging Center at the University of Groningen; Henriette Arts and Ate van der Zee of the division of gynaecological oncology at the University of Groningen; and Joost Bart of the Department of Pathology and Molecular Biology of the University Medical Center of Groningen.

Low is the chief science officer for Endocyte Inc., a Purdue Research Park-based company that develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte holds the license to the folate receptor-targeting technology and is spinning this technology off into a new company called OnTarget.

Ntziachristos led the team at the Technical University of Munich that developed the camera system. A startup company named SurgOptix BV is working to commercialize the camera system.

The clinical trial was funded by Endocyte Inc. and the University Medical Center of Groningen.

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Women Who Inherit BRCA Gene Mutations Develop Cancer Earlier than their Ancestors

September 12 2011

A new analysis has found that women who develop certain hereditary cancers develop them at earlier ages than women in the previous generation. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the results point to the importance of tracking younger ages of cancer diagnosis to determine when to provide counseling, screening, and treatment services.

Women who have mutations in the BRCA genes have a high risk of developing breast and ovarian cancers at young ages. Mutations in these genes are often inherited, so multiple family members may be diagnosed with these cancers at young ages. Researchers have wondered: if a woman develops BRCA-related cancer at a certain age, will female relatives in the next generation develop it even earlier?

To investigate, Jennifer Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues looked at trends in the age of cancer diagnosis between generations in families with a history of BRCA-related cancer. Of 132 women in the study who had breast cancer and BRCA gene mutations, 106 had a family member in the previous generation who was diagnosed with a BRCA-related cancer (either breast or ovarian cancer).

When evaluating age differences between generations in each family, the researchers found that the average age of cancer diagnosis in the second generation was 42 years, compared with 48 years in the first generation. A separate more inclusive analysis of the entire study group revealed that the expected age-of-onset of cancer went down by 7.9 years from the first generation to the second.

The results suggest that women who inherit BRCA gene mutations develop cancer at younger ages than women in the previous generation.

Guidelines by the National Comprehensive Cancer Network suggest initiating screening for hereditary breast cancer at age 25 years or five to ten years earlier than the age of earliest diagnosis in a family. “Our research tells us that we need to continue to initiate screenings at least ten years prior to the earliest cancer diagnosis,” said Dr. Litton. “Also, because we do not have the BRCA mutation status of affected individuals from previous generations, when testing may not have been available yet, it is vital that we continue to collect family information,” she added. Monitoring for shifts in the age of cancer diagnosis in future generations will help caregivers and patients decide when to consider counseling, screening, and treatments.

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Patients' Underlying Health Linked to Worse Outcomes for Melanoma

August 30 2011

It's not how old but how frail patients are that can predict how well they will fare after a melanoma diagnosis. In fact, young patients in poor health may have worse outcomes than older patients in good shape.

A new study from the University of Michigan Comprehensive Cancer Center finds that patients with decreased core muscle density were more likely to see their cancer spread to distant parts of the body.

These findings may also support the idea that the patient's biological response to a tumor is important in controlling the spread of melanoma. Patients whose systems are less able to mount a response may be more prone to their cancer spreading.

The researchers believe that identifying those patients who are at higher risk of poor outcomes could impact treatment decisions, including the success of new immunotherapy drugs. And potentially, if this degenerative muscle loss, called sarcopenia, can be reversed, patients might have better outcomes.

The study, which appears online in Annals of Surgical Oncology, looked at 101 patients treated for stage III melanoma at the U-M Comprehensive Cancer Center. Researchers examined CT scans for each patient to measure the area and density of a core muscle called the psoas, which runs along both sides of the spine.

They found that patients with lower muscle density had significantly higher rates of their cancer returning – regardless of factors such as the size of the tumor or the patient's age. Every 10 units of decreased muscle density translated to a 28% increase in recurrence. In addition, frailer patients had more complications from surgery to remove their cancerous lymph nodes.

Research has previously linked older age to worse outcomes in melanoma. These new results distinguish that it'’s the underlying vitality of the patient, not age, that really matters.

Many studies have looked at ways to reverse sarcopenia by focusing on diet and exercise.

"The big question is if we could reverse sarcopenia through better nutrition and exercise, would that lead to a decreased risk of recurrence in those patients?" says lead study author Michael Sabel, MD, associate professor of surgery at the U-M Medical School.

In addition, researchers hope this information will help explain the limited success of new immunotherapy or cancer vaccine treatments.

"The data suggests that frailer patients may be less likely to respond to these forms of therapy. It is very possible that prior trials of vaccines or other immune therapies that didn't show an effect would have shown an effect if we had weeded out the patients unlikely to respond to therapy," Sabel says.

Researchers plan next to look at CT scans from patients treated in these trials to analyze whether the treatments were more effective in patients without sarcopenia.

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Adjuvant Therapy May Not Be Necessary for Older Breast Cancer Patients

August 31 2011

Breast cancer patients over the age of 60 with early-stage, hormone-responsive small tumors who forego adjuvant endocrine, also called hormonal therapy, are not at an increased risk of mortality compared to women of the same age without breast cancer, according to a study published August 31, 21011, in the Journal of the National Cancer Institute.

The use of hormonal therapy has increased in breast cancer patients overall, and the 2009 St. Gallen International Breast Cancer Conference recommended hormonal therapy for almost all patients with hormone-responsive disease. But previous studies have not identified patient subgroups that might not need adjuvant therapy or those who without the therapy would have the same longevity as women in the general population.

To identify patient sub-groups who may or may not benefit from adjuvant hormone therapy, Peer Christiansen, MD, of the Aarhus University Hospital in Denmark and colleagues, looked at a population-based cohort of untreated breast cancer patients in Denmark. They identified 3197 patients with node-negative breast cancer from the Danish Breast Cancer Cooperative Group, between the ages of 35 and 74. The patients were not given adjuvant hormone therapy or chemotherapy. 

The researchers obtained data on the mortality rate of the general Danish female population from Statistics Denmark. The researchers then estimated the relative risk of death among women in the study compared to the general population by calculating the standardized mortality ratios, or the ratio of the observed number of deaths among patients in the cohort compared to the expected number of deaths in the general population.

The researchers found that the excess mortality rate in the patient population was highest for patients aged between 35 and 39 years and lowest for those aged 60-64 years. The relative mortality of patients compared to the general population was also greater for patients with tumors larger than 10 millimeters. The researchers write: “Age less than 60 years at diagnosis and tumor size greater than 10 millimeters were independently associated with a worse prognosis.”

However, they also identified a group of low-risk patients aged 60 or older with mortality rates comparable to the general population. These patients had tumors or 10 millimeters or less and low-grade disease (grade 1 ductal carcinoma, or grade 1 or 2 invasive lobular carcinoma.) The researchers concluded that these patients might not benefit from adjuvant therapy.

In an accompanying editorial, Jennifer J. Griggs, MD, MPH, and Daniel F. Hayes, MD, of the University of Michigan, write that the study confirms findings from other studies showing that local therapy alone is adequate for treating older women with small tumors and that “adjuvant endocrine therapy does not reduce the risk of mortality in patients with very small, node-negative hormone receptor-positive breast cancer because the risk of mortality is already extremely low.”

However, the editorialists add that overall adjuvant therapy is effective in reducing the risk of recurrence in the same or opposite breast and that many women will continue to take it for that reason. “Clearly, patient preferences regarding risks and benefits of endocrine therapy play a critical role in decision making, and high-quality information support is essential in these settings.”

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FDA Approves Xalkori with Companion Diagnostic for a Type of Late-stage Lung Cancer

Second targeted therapy approved with a test this year

August 26 2011

The U.S. Food and Drug Administration has approved Xalkori (crizotinib) to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene.

Xalkori is being approved with a companion diagnostic test that will help determine if a patient has the abnormal ALK gene, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit. It is the second such targeted therapy approved by the FDA this year.

This ALK gene abnormality causes cancer development and growth. About 1 percent to 7 percent of those with NSCLC have the ALK gene abnormality. Patients with this form of lung cancer are typically non-smokers. Xalkori works by blocking certain proteins called kinases, including the protein produced by the abnormal ALK gene. Xalkori is a pill taken twice a day as a single-agent treatment.

“The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.”

Xalkori’s safety and effectiveness were established in two multi-center, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. A sample of a patient’s lung cancer tissue was collected and tested for the ALK gene abnormality prior to study enrollment. The studies were designed to measure objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.

In one study, the objective response rate was 50 percent with a median response duration of 42 weeks. In another, the objective response rate was 61 percent with a median response duration of 48 weeks.

The FDA based its approval of the Vysis ALK Break Apart FISH Probe Kit on data from one of the studies.

Xalkori was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists.

Xalkori is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, followed by further studies to confirm the drug’s clinical benefit.

Xalkori and the companion Vysis ALK Break Apart FISH Probe Kit were approved ahead of the drug’s Sept. 30, 2011, FDA review goal date and the companion diagnostics’ Sept. 28, 2011, review goal date.

“The trend in oncology research continues towards targeted therapies,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health. “This test is an example of the important role companion diagnostics play in determining that the safest and most effective treatments are promptly delivered to patients living with serious and life-threatening diseases.”

The most common side effects reported in patients receiving Xalkori included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects. Xalkori use has also been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. Patients with treatment-related pneumonitis should permanently stop treatment with Xalkori. The drug should not be used in pregnant women.

In July 2011, FDA issued a draft guidance industry on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy. The guidance is currently available for public comment.

Xalkori is marketed by New York City-based Pfizer. The Vysis ALK Break Apart FISH Probe Kit is marketed by Abbott Molecular Inc. of Des Plaines, Ill.

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UCSF Study Shows Greater Impact of Chemotherapy on Fertility

August 24 2011

Current estimates of the impact of chemotherapy on women’s reproductive health are too low, according to a University of California, San Francisco (UCSF) study. The researchers say their analysis of the age-specific, long-term effects of chemotherapy provides new insights that will help patients and clinicians make more informed decisions about future reproductive options, such as egg harvesting.

Previous studies largely have focused on amenorrhea, or the lack of menstruation shortly after treatment, as the primary reproductive side effect of chemotherapy. In this analysis, the researchers also focused on longer-term, age-specific outcomes associated with chemotherapy, including infertility and early menopause. They also noted that the younger a woman is when diagnosed with cancer, the more likely she will experience early menopause.

“We found chemotherapy essentially narrows a woman’s reproductive window by causing a range of damage to the ovaries, even if her menses resume after chemotherapy,” said Mitchell Rosen, MD, senior author and assistant professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences. 

Many of the women who responded to the survey had been told that as long as their periods came back, they would have no negative impact from treatment, he said.

“We currently make recommendations on preserving fertility based on limited data. These new findings, which also take into account cancer type and age, hopefully will enable us to offer more strategic and personalized counseling,” said Rosen, who also is director of the UCSF Fertility Preservation Center.

The study is available online in the journal Cancer. The researchers used the California Cancer Registry, a statewide population-based cancer surveillance system, to ask women about their reproductive history before and after cancer treatment. Survey questions addressed acute ovarian failure (cessation of menses after treatment), early menopause (menopause before 45 years old), and infertility (failed conception).

A total of 1,041 women diagnosed with one of five targeted cancers between the ages of 18 and 40 years old responded, and 620 reported having been treated with only chemotherapy. The five cancer types – leukemia, Hodgkin’s disease, non-Hodgkin lymphoma, breast cancer and gastrointestinal cancers – were chosen because they are common non-gynecologic cancer groups that can be treated with systemic chemotherapy. Key findings include:

• The percentage of women reporting acute ovarian failure was 8 percent, 10 percent, 9 percent and 5 percent for Hodgkin’s disease, non-Hodgkin lymphoma, breast cancer, and gastrointestinal cancers respectively. Acute ovarian failure increased significantly with age at diagnosis. 
• In women without acute ovarian failure, the incidence of infertility increased significantly with age at diagnosis. For instance, the proportion of infertile women with Hodgkin’s disease was 18 percent at 20 years old and 57 percent at 35 years old.
• The estimated probability of early menopause increased significantly with younger age at diagnosis. For example, using age as a predictor of early menopause in non-Hodgkin lymphoma, 56 percent of women 20 years old at diagnosis may experience menopause early, compared to 16 percent of those who were 35 years old at diagnosis.

Approximately 120,000 women younger than age 50 develop cancer each year in the United States, according to statistics from the 2006 Surveillance, Epidemiology, and End Results (SEER), and several studies show that loss of reproductive potential after cancer treatment can negatively impact quality of life in young survivors.

While 7 percent of women across the United States report 12-month infertility according to the researchers, the rates of infertility in young cancer patients are unknown.

“We noted proportions of infertility among cancer survivors that appear considerably higher than those in the general United States population,” said Joseph Letourneau, MD, the study’s lead author. Letourneau was a medical student under Rosen when the research was conducted and now works as a resident physician in obstetrics and gynecology at the University of North Carolina. “When counseling patients, focusing solely on short-term outcomes like loss of menses may give women unrealistically low assessments of their risks, since they could experience infertility or early menopause years to decades after treatment.”

Rosen said that more research is needed since the retrospective study did not include specific patient characteristics such as genetics or variations in individual cancer treatments.

“Our analysis adds one more piece to the puzzle,” he said. “Doctors will continue to need to use their gestalt and understanding of a patient’s life to provide the best guidance.”

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Use of Radioactive Iodine for Treatment of Thyroid Cancer on the Rise

August 16 2011

CHICAGO — Despite uncertainty about the appropriate use of radioactive iodine after surgery for different stages of thyroid cancer, between 1990 and 2008 its use has increased among patients with all tumor sizes, and there was wide variation in use of this treatment among hospitals, according to a study in the August 17 issue of JAMA.

"More than 40,000 individuals in the United States receive a thyroid cancer diagnosis each year, and the overwhelming majority of cases are well-differentiated thyroid cancer. Standard treatment for well-differentiated thyroid cancer is thyroidectomy. To ensure full eradication of remnant thyroid tissue and to treat residual disease in patients with visible, inoperable, iodine-avid metastases, radioactive iodine is often administered after total thyroidectomy," according to background information in the article. Previous studies have shown improved survival and reduced tumor recurrence when advanced-stage, well-differentiated thyroid cancer is treated with radioactive iodine. "In contrast, for very low-risk disease, in which prognosis is typically excellent, treatment with radioactive iodine is of uncertain benefit."

Megan R. Haymart, MD, of the University of Michigan, Ann Arbor, Mich., and colleagues conducted a study to determine changes in practice patterns regarding the use of radioactive iodine following thyroidectomy and examined the degree to which hospitals vary in their use of radioactive iodine. The analysis included 189,219 patients with well-differentiated thyroid cancer treated at 981 hospitals associated with the U.S. National Cancer Database between 1990 and 2008.

The researchers found that during this time period there was a significant increase, across all tumor sizes, in the proportion of patients with well-differentiated thyroid cancer who received radioactive iodine as therapy after total thyroidectomy. In 1990, 1,373 (40.4 percent) of 3,397 patients received radioactive iodine whereas in 2008, 11,539 (56.0 percent) of 20,620 received radioactive iodine. Analysis indicated that younger age and absence of comorbidity were associated with a small but significantly greater likelihood of receiving radioactive iodine after total thyroidectomy. Also, female sex, African American race, and absence of private/government insurance were associated with significantly less likelihood of receiving radioactive iodine.

The researchers also found that there was a statistically significant difference in radioactive iodine use between American Joint Committee on Cancer stages I and IV, but not for stage II or III vs. stage IV. When hospital case volume was analyzed, there was an increased likelihood of radioactive iodine use as the volume of thyroid cancer cases treated at a hospital increased.

"Wide variation in radioactive iodine use existed, and only 21.1 percent of this variation was accounted for by patient and tumor characteristics. Hospital type and case volume accounted for 17.1 percent of the variation. After adjusting for available patient, tumor, and hospital characteristics, 29.1 percent of the variance was attributable to unexplained hospital characteristics," the authors write. "This finding suggests disease severity is not the sole determinant of radioactive iodine use."

"...the results of this study have implications for patients, physicians, and payers. Although it is appropriate therapy for certain well-differentiated thyroid cancers, the benefit of radioactive iodine may not always exceed the risks. There is a clear role for adjuvant therapy with radioactive iodine in iodine-avid, advanced-stage, well-differentiated thyroid cancer; however, there is unclear benefit to radioactive iodine use in low-risk disease because patients with low-risk disease have an excellent prognosis regardless of intervention. In addition to clear cost-saving benefits associated with not using radioactive iodine for low-risk disease, limiting radioactive iodine use would decrease patients' risks of adverse effects. Not only are there transient adverse effects on quality of life with the hypothyroidism typically required before radioactive iodine treatment, but radioactive iodine itself has long-term health risks."

The researchers add that the "fact that disease severity appears to have a small influence on radioactive iodine use after thyroid surgery is concerning. In the interest of curbing the increasing health care costs and preventing both over-treatment and under-treatment of disease, indications for radioactive iodine should be clearly defined and disease severity should become the primary driver of radioactive iodine use."

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FDA Approves Zelboraf (Vemurafenib) and Companion Diagnostic for BRAF Mutation-Positive Metastatic Melanoma, a Deadly Form of Skin Cancer

August 17 2011

South San Francisco, Calif. -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved ZelborafTM (vemurafenib) for the treatment of BRAF V600E mutation-positive, inoperable or metastatic melanoma, as determined by an FDA-approved test. The FDA today also approved the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche to identify patients eligible for treatment. Zelboraf is the first and only FDA-approved personalized medicine shown to improve survival in people with BRAF V600E mutation-positive metastatic melanoma, demonstrating the benefits of Roche's personalized healthcare approach. It is designed to target and inhibit some mutated forms of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.

"The FDA approval of Zelboraf marks a major step forward in personalizing the treatment of metastatic melanoma, a devastating disease that until this year had limited approved treatment options," said Hal Barron, MD, chief medical officer and head, Global Product Development. "We will continue to study this medicine with a goal of further improving outcomes for people with melanoma and other cancers that are driven by BRAF mutations."

Zelboraf should be used only in people whose inoperable or metastatic melanoma carries a BRAF V600E mutation, which can be determined by the FDA-approved cobas BRAF Mutation Test.

"The cobas BRAF Mutation Test has improved sensitivity, accuracy and speed compared to other commonly used, unapproved detection methods," said Paul Brown, head of Roche Molecular Systems. "With a personalized medicine now available, all people diagnosed with inoperable or metastatic melanoma should be tested to help determine the best options for treatment."

Zelboraf will be available in the United States within two weeks of approval and will be distributed through specialty pharmacies (mail-order pharmacies). For more information about Zelboraf distribution, doctors can contact Zelboraf Access Solutions (http://www.GenentechAccessSolutions.com or 1-888-249-4918). Zelboraf Access Solutions also provides doctors and patients coverage and reimbursement support, patient assistance and information resources.

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Music Reduces Anxiety in Cancer Patients

August 10 2011

Cancer patients may benefit from sessions with trained music therapists or from listening to music. A new Cochrane systematic review shows using music can reduce anxiety in cancer patients, and may also have positive effects on mood, pain and quality of life.

Music and music therapy are used in a wide range of clinical settings. Treatments range from patients listening to pre-recorded music, to music therapists engaging patients in music experiences to improve psychological and physical well-being. In the review, researchers focused on trials with patients with any kind of cancer who were offered music or music therapy sessions.

The researchers analysed evidence from 1,891 patients taking part in 30 trials. 13 trials used trained music therapists, while in the remaining 17 trials, patients listened to pre-recorded music. How long and how often patients participated in music sessions varied greatly among trials. The results show that compared to standard treatments, music reduced anxiety considerably based on clinical anxiety scores. Some trials reported much larger beneficial effects than others. The results also suggest that music therapy may increase patients’ quality of life. There was some benefit in music for mood and pain, although not depression. Smaller beneficial effects were seen for heart rate, respiratory rate and blood pressure.

“The evidence suggests that music interventions may be useful as a complementary treatment to people with cancer,” said lead researcher Joke Bradt of the Department of Creative Arts Therapies at Drexel University in Philadelphia, US. “Music interventions provided by trained music therapists as well as listening to pre-recorded music both have shown positive outcomes in this review, but at this time there is not enough evidence to determine if one intervention is more effective than the other.”

“It should be noted, however, that when patients can’t be blinded to an intervention, there is an opportunity for bias when they are asked to report on subjective measures like anxiety, pain mood and quality of life,” said Bradt.

The researchers point out that the quality of evidence for some outcomes was low because of the small numbers of trials that have been carried out. Further trials could help increase certainty in the findings and improve understanding of music’s impact on distress, body image and other aspects, for which research is currently too scarce to draw any conclusions.

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Genetically Modified "Serial Killer" T Cells Obliterate Tumors in Patients with Chronic Lymphocytic Leukemia, Penn Researchers Report

August 10 2011

PHILADELPHIA -- In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania's Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T cells. The protocol, which involves removing patients' cells and modifying them in Penn's vaccine production facility, then infusing the new cells back into the patient's body following chemotherapy, provides a tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma. The findings, published simultaneously today in the New England Journal of Medicine and Science Translational Medicine, are the first demonstration of the use of gene transfer therapy to create "serial killer" T cells aimed at cancerous tumors.

"Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected," said senior author Carl June, MD, director of Translational Research and a professor of Pathology and Laboratory Medicine in the Abramson Cancer Center, who led the work. "It worked much better than we thought it would."

The results of the pilot trial of three patients are a stark contrast to existing therapies for CLL. The patients involved in the new study had few other treatment options. The only potential curative therapy would have involved a bone marrow transplant, a procedure which requires a lengthy hospitalization and carries at least a 20 percent mortality risk -- and even then offers only about a 50 percent chance of a cure, at best.

"Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them," says co-principal investigator David Porter, MD, professor of Medicine and director of Blood and Marrow Transplantation. "This approach has the potential to do the same thing, but in a safer manner."

Secret Ingredients
June thinks there were several "secret ingredients" that made the difference between the lackluster results that have been seen in previous trials with modified T cells and the remarkable responses seen in the current trial. The details of the new cancer immunotherapy are detailed in Science Translational Medicine.

After removing the patients' cells, the team reprogrammed them to attack tumor cells by genetically modifying them using a lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T cells and designed to bind to a protein called CD19.

Once the T cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL tumor cells and normal B cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T cells, which limits side effects typically experienced during standard therapies.

The team engineered a signaling molecule into the part of the CAR that resides inside the cell. When it binds to CD19, initiating the cancer-cell death, it also tells the cell to produce cytokines that trigger other T cells to multiply -- building a bigger and bigger army until all the target cells in the tumor are destroyed.

Serial Killers
"We saw at least a 1000-fold increase in the number of modified T cells in each of the patients. Drugs don't do that," June says. "In addition to an extensive capacity for self-replication, the infused T cells are serial killers. On average, each infused T cell led to the killing of thousands of tumor cells – and overall, destroyed at least two pounds of tumor in each patient."

The importance of the T cell self-replication is illustrated in the New England Journal of Medicine paper, which describes the response of one patient, a 64-year old man. Prior to his T cell treatment, his blood and marrow were replete with tumor cells. For the first two weeks after treatment, nothing seemed to change. Then on day 14, the patient began experiencing chills, nausea, and increasing fever, among other symptoms. Tests during that time showed an enormous increase in the number of T cells in his blood that led to a tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.

By day 28, the patient had recovered from the tumor lysis syndrome –– and his blood and marrow showed no evidence of leukemia.

"This massive killing of tumor is a direct proof of principle of the concept," Porter says.

The Penn team pioneered the use of the HIV-derived vector in a clinical trial in 2003 in which they treated HIV patients with an antisense version of the virus. That trial demonstrated the safety of the lentiviral vector used in the present work.

The cell culture methods used in this trial reawaken T cells that have been suppressed by the leukemia and stimulate the generation of so-called "memory" T cells, which the team hopes will provide ongoing protection against recurrence. Although long-term viability of the treatment is unknown, the doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their seek-and-destroy mission against cancerous cells throughout the patients’ bodies.

Moving forward, the team plans to test the same CD19 CAR construct in patients with other types of CD19-positive tumors, including non-Hodgkin's lymphoma and acute lymphocytic leukemia. They also plan to study the approach in pediatric leukemia patients who have failed standard therapy. Additionally, the team has engineered a CAR vector that binds to mesothelin, a protein expressed on the surface of mesothelioma cancer cells, as well as on ovarian and pancreatic cancer cells.

In addition to June and Porter, co-authors on the NEJM paper include Bruce Levine, Michael Kalos, and Adam Bagg, all from Penn Medicine. Michael Kalos and Bruce Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include June, Porter, Sharyn Katz and Adam Bagg from Penn and Stephan Grupp the Children's Hospital of Philadelphia.

The work was supported by the Alliance for Cancer Gene Therapy, a foundation started by Penn graduates Barbara and Edward Netter, to promote gene therapy research to treat cancer, and the Leukemia & Lymphoma Society.

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Vitamin D Relieves Joint, Muscle Pain for Breast Cancer Patients

July 26 2011

High-dose vitamin D relieves joint and muscle pain for many breast cancer patients taking estrogen-lowering drugs, according to a new study from Washington University School of Medicine in St. Louis.

The drugs, known as aromatase inhibitors, are commonly prescribed to shrink breast tumors fueled by the hormone estrogen and help prevent cancer recurrence. They are less toxic than chemotherapy, but for many patients, the drugs may cause severe musculoskeletal discomfort, including pain and stiffness in the hands, wrists, knees, hips, lower back, shoulders and feet.

“About half of patients can experience these symptoms,” says Antonella L. Rastelli, MD, assistant professor of medicine and first author of the study published online in the journal Breast Cancer Research and Treatment. “We don’t know exactly why the pain occurs, but it can be very debilitating — to the point that patients decide to stop taking aromatase inhibitors.”

Because the drugs reduce cancer recurrence, finding a way to help patients stay on them is important for long-term, relapse-free survival, according to Rastelli. Aromatase inhibitors are prescribed to post-menopausal women for at least five years and often longer after a breast cancer diagnosis. There is some evidence that patients who experience the drugs’ side effects are less likely to see their cancer return, providing even more incentive to help these patients continue taking them.

It was Rastelli’s colleague, Marie E. Taylor, MD, assistant professor of radiation oncology, who first noticed that patients on aromatase inhibitors who experienced this pain found some relief from high doses of vitamin D.

So Rastelli’s group recruited 60 patients who reported pain and discomfort associated with anastrozole, one of three FDA-approved aromatase inhibitors. The patients they studied also had low vitamin D levels. Half the group was randomly assigned to receive the recommended daily dose of vitamin D (400 international units) plus a 50,000-unit vitamin D capsule once a week. The other half received the daily dose of 400 units of vitamin D plus a weekly placebo. All subjects received 1,000 milligrams of calcium daily throughout the study.

Patients in the study reported any pain they experienced through three different questionnaires. They were asked to quantify their pain intensity, as well as report how much the pain altered their mood, affected their work and interfered with relationships and daily activities. The results show that patients receiving high-dose vitamin D every week reported significantly less musculoskeletal pain and also were less likely to experience pain that interfered with daily living.

“High-dose vitamin D seems to be really effective in reducing the musculoskeletal pain caused by aromatase inhibitors,” Rastelli says. “Patients who get the vitamin D weekly feel better because their pain is reduced and sometimes goes away completely. This makes the drugs much more tolerable. Millions of women worldwide take aromatase inhibitor therapy, and we may have another ‘tool’ to help them remain on it longer.”

Like anastrozole used in this study, the other two FDA-approved aromatase inhibitors, letrozole and exemestane, also cause musculoskeletal pain. Given the similar side effects, Rastelli says patients on these drugs may also benefit from high-dose vitamin D.

The vitamin used in this study is a plant-derived type called vitamin D2. Rastelli says it achieves the best results when given weekly because the body metabolizes it within seven to 10 days. Rastelli and her colleagues did not use high-dose vitamin D3, which remains in the body longer.

“This was a very carefully conducted study, and the placebo control makes the findings quite compelling,” says Matthew J. Ellis, MD, PhD, the study’s senior author and director of the Breast Cancer Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis. “We should follow up these findings further to determine the most efficacious and safe approach to vitamin D supplementation in our breast cancer patients.”

Since vitamin D helps the body absorb calcium, too much of it can cause high levels of calcium in the urine, which may increase the risk of kidney stones. Such possible side effects emphasize the importance of tracking patients’ urine calcium levels while taking high-dose vitamin D.

“It’s important to monitor the patients, but overall it appears to be very safe,” Rastelli says. “Because vitamin D2 is eliminated from the body so quickly, it’s very hard to overdose.”

In addition to relieving pain, the group wanted to examine whether vitamin D could protect against the bone loss often seen in patients taking aromatase inhibitors. The researchers measured each patient’s bone density at the beginning of the study and again after six months.

Perhaps because of its role in calcium absorption, high-dose vitamin D did appear to help maintain bone density at the neck of the femur, the top of the thighbone near the hip joint. Although the result did not reach statistical significance, Rastelli calls the result promising and worth further studies.

“It’s great that we have something as simple as vitamin D to help patients alleviate some of this pain,” Rastelli says. “It’s not toxic — it doesn’t cause major side effects. And if it is actually protecting against bone loss, that’s even better.”

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Cancer Patients Need Extra Sun Safety, UAB Experts Say

July 28 2011

Summer often brings with it fun in the sun, but for cancer patients it also presents new challenges and the need for additional protection.

“Cancer patients may be more at risk for sun damage because of their treatment,” says Elizabeth Kvale, MD, director of outpatient supportive care and survivorship in the Department of Medicine at University of Alabama at Birmingham and associate scientist in the UAB Comprehensive Cancer Center.

Cancer patients should adhere to the basic sun-protection guidelines: Wear sunscreen and protective clothing in the hot, summer months. The American Society of Clinical Oncologists (ASCO) recommends skin cancer patients also should take special care to protect areas of skin being treated; dark, tightly woven fabrics are most effective.

“Skin that has been treated with radiation therapy may lose some of its natural protective capacity because of the changes that occur with treatment,” says Kvale. “Radiation-exposed skin should be completely protected from sun exposure.”

Patients receiving chemotherapy also are more sensitive to the sun’s rays. Kvale says it is important to cover surgical scars because they may darken if exposed to the sun, and patients who lose their hair during treatment should protect the scalp because it can burn easily.

“Pediatric cancer patients, survivors and their caregivers should be especially attentive to sun safety,” adds Kvale. Studies have shown that extended exposure to the sun is linked to the development of skin cancers for everyone, and children have a significantly elevated risk of developing serious skin cancer as a long-term consequence from sunburn.

Heat is also an enemy to cancer patients, who may be more susceptible to dehydration or heat exhaustion from side-effects of cancer treatment, such as vomiting, diarrhea and nausea. Patients should drink fluids throughout the day, chew on ice chips to relieve dry mouth, avoid beverages with alcohol or caffeine and eat fruits and vegetables with high fluid content.

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Breast Density Tied to Specific Types of Breast Cancer

July 27 2011

Women with breasts that appear dense on mammograms are at a higher risk of breast cancer and their tumors are more likely to have certain aggressive characteristics than women with less dense breasts, according to a study published online July 27, 2011, in the Journal of the National Cancer Institute.

Mammographic breast density – a reflection of the proportions of fat, connective tissue, and epithelial tissue in the breast – is a well-established risk factor for breast cancer. Women with higher amounts of epithelial and stromal tissue have higher density and higher risk. However, it has not been clear whether breast density was associated with specific tumor characteristics and tumor type.

To explore this issue, Rulla M. Tamimi, ScD, at Harvard  Medical School and Brigham and Women’s Hospital, Boston, and colleagues, compared breast density in 1,042 postmenopausal women with breast cancer and 1,794 matched control subjects (women who were similar in terms of age, postmenopausal hormone use, and other factors, but did not have breast cancer).

The researchers found, as expected, that the risk of breast cancer increased progressively with increasing breast density. The associations were stronger for larger tumors than for smaller tumors; for high-grade than for low-grade tumors; and for estrogen receptor-negative than for estrogen receptor-positive tumors. The link between density and breast cancer also appeared to be stronger for ductal carcinoma in situ (DCIS) than for invasive tumors. There was no association, however, between density and other markers of tumor aggressiveness, such as nodal involvement and HER2 status.

The authors conclude that higher mammographic density is associated with more aggressive tumor characteristics and also with DCIS. “Our results suggest that breast density influences the risk of breast cancer subtypes by potentially different mechanisms,” they write. “Further studies are warranted to explain underlying biological processes and elucidate the possible pathways from high breast density to the specific subtypes of breast carcinoma.”

An accompanying editorial agrees that understanding the biological links between breast density and specific tumor subtypes could help us understand more about breast cancer risk and the molecular causes of breast cancer.  Karla Kerlikowske, MD, of the University of California, San Francisco and Amanda Phipps, PhD, of Fred Hutchinson Cancer Research Center in Seattle emphasize that this large study was the first to find a stronger association between breast density and ER-negative tumors than ER-positive tumors.

They caution, however, that this stronger association might be due, in part, to the ‘masking effect.’  “Masking of a tumor can occur because cancerous tissue and mammographically dense tissue have similar x-ray attenuation, allowing tumors to go undetected on screening mammography examination and progress to a more advanced and aggressive stage before detection,” they write. In this study, it is not known whether the tumors were detected by screening mammography.

The editorialists also discuss other possible reasons for the strong link between density and aggressive tumors, including the interaction of increased numbers of stromal and epithelial cells in dense breasts and exposure to postmenopausal hormones. 

They conclude that breast density is an important risk factor for diverse subtypes of breast cancer. “Given that the magnitude of the association with breast density is strong across all breast cancer subtypes and particularly for ER-negative disease, breast density should be included in risk prediction models across tumor subtypes,” they write.  

      

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Erlotinib Nearly Triples Progression-free Survival Compared with Standard Chemotherapy in Patients with the Most Common Form of Lung Cancer

July 21 2011

The targeted drug erlotinib nearly triples progression-free survival (PFS), and is better tolerated, compared with standard chemotherapy as the initial treatment for patients with advanced non-small-cell lung cancer (NSCLC) whose tumours harbour epidermal growth factor receptor (EGFR) mutations. The results, published Online First in The Lancet Oncology, suggest that erlotinib should be one of the first-line treatments now considered for advanced NSCLC in patients with activating EGFR mutations.

Despite progress in recent years, lung cancer remains the leading cause of cancer death worldwide. Increasingly, research has focused on identifying potential biomarkers to prolong survival from new targeted drugs and optimise treatment decisions for individual patients. To date, the most promising of these markers is EGFR mutation status. Previous studies have shown that NSCLC patients with EGFR mutations respond well to tyrosine kinase inhibitor (TKI) therapies such as erlotinib.

The OPTIMAL study is the first phase 3 trial to examine whether erlotinib has comparable efficacy and safety to chemotherapy in patients whose lung cancer harbours EGFR mutations. 165 patients were recruited from 22 centres across China and randomly assigned to erlotinib (83 patients) or a standard platinum chemotherapy regimen of gemcitabine and carboplatin (82).

Erlotinib significantly prolonged median PFS compared with chemotherapy (13.1 months vs 4.6 months).

Serious treatment-related side-effects were only reported in 2% of patients treated with erlotinib compared with 14% given chemotherapy. Grade 3 and 4 toxic effects were also more common in patients receiving chemotherapy, with 42% of patients experiencing neutropenia (low white blood count) and 40% thrombocytopenia (abnormally low number of platelets in the blood) compared with no patients taking erlotinib. The most frequently reported grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (4%) and skin rash (2%).

The authors say: “To our knowledge, OPTIMAL is the first phase 3 study to show that patients with EGFR mutation-positive NSCLC who receive erlotinib can live for more than a year without disease progression and also clearly shows the clinical usefulness of testing for a molecular biomarker in lung cancer to guide treatment and improve patient outcomes.”

They conclude: “We recommend that EGFR TKIs be regarded as the first-line treatment of choice for this subgroup of patients and chemonaive patients should undergo EGFR mutation testing wherever possible.”

In a Comment, Tetsuya Mitsudomi from Aichi Cancer Center Hospital, Nagoya, Japan says: “OPTIMAL clearly shows the importance of EGFR mutation testing and patient selection according to these test results for use of erlotinib…EGFR TKIs are undoubtedly key drugs for patients with EGFR mutations and should be used early in treatment. However, when EGFR test results cannot be obtained in a reasonably short timeframe, first-line chemotherapy and second-line EGFR TKI after progression is a reasonable option if the patient is later shown to be EGFR mutation-positive.”

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Trastuzumab and Chemotherapy Improved Survival in HER2-postive Breast and Brain Cancer Patients

July 18 2011

PHILADELPHIA — The use of trastuzumab, chemotherapy and surgery among women with HER2-positive metastatic breast cancer significantly improved survival from the time central nervous system metastases were diagnosed.

Based on these study results, lead researcher Adam Brufsky, MD, PhD, said, “We clearly now know that these women should get trastuzumab and potentially chemotherapy, even if cancer spreads to the brain.”

“Women with HER2-positive breast cancer have a reasonable chance of living a long time with their disease, and they should be given aggressive therapy where appropriate,” added Brufsky, professor of medicine and associate director of clinical investigation at the University of Pittsburgh Cancer Institute.

Ten to 16 percent of women with advanced breast cancer develop central nervous system metastases, the researchers wrote in their study, published in Clinical Cancer Research, a journal of the American Association for Cancer Research. Brufsky and colleagues used data from the registHER study to evaluate the incidence, potential risk factors and outcomes for patients with HER2-positive breast cancer. They evaluated how patients with HER2-positive breast cancer develop brain metastases, and followed them to examine what happens thereafter.

Of the 1,023 women newly diagnosed with HER2-positive metastatic breast cancer, 377 had central nervous system metastases.

Patients with central nervous system metastases were younger, and more likely to have hormone receptor–negative disease and higher disease burden compared with those whose cancer did not spread to the brain. In addition, for those patients without central nervous system metastases at initial diagnosis, cancer progressed to the brain about 13 months after diagnosis.

For those diagnosed with central nervous system metastases, treatment with trastuzumab, chemotherapy or surgery was each associated with a significant improvement in overall survival: trastuzumab 17.5 months vs. no trastuzumab 3.8 months; chemotherapy 16.4 months vs. no chemotherapy 3.7 months; and surgery 20.3 months vs. no surgery 11.3 months.

“It is surprising that chemotherapy/trastuzumab adds to these women’s survival,” Brufsky said. “We thought that the brain metastases would be dominant in this regard no matter what therapy.”

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Intermediate-grade Prostate Cancer NIH-funded Study Shows Reduction with Use of Short-term Hormone Therapy Plus Radiation Therapy

July 13 2011

Short-term hormone therapy given in combination with radiation therapy to men with early-stage prostate cancer increased their chances of living longer compared to treatment with radiation therapy alone, according to a clinical trial supported by the National Cancer Institute (NCI), part of the National Institutes of Health.  Benefits of the combined treatment were limited mainly to patients with intermediate-risk disease and were not seen for men with low-risk prostate cancer, researchers say. The results appeared in the July 14, 2011, New England Journal of Medicine. The trial was conducted by the Radiation Therapy Oncology Group.

The study, the largest randomized trial of its kind, enrolled nearly 2,000 men with low-and intermediate-risk prostate cancer and followed their health status for more than nine years at 212 centers in the United States and Canada.  All study participants had localized, or non-metastatic, prostate cancer and serum prostate-specific antigen (PSA) levels of less than 20 nanograms per milliliter.  PSA levels of less than 20, along with normal blood tests and a normal bone scan, indicate that the cancer is low or intermediate risk.  Patients were randomly assigned to treatment with radiation alone or radiation plus short-term androgen deprivation therapy (ADT) using drugs that drastically lowered their natural production of testosterone, a hormone which feeds prostate cancer growth.   

In addition to investigating whether the participants lived longer on one therapy compared to another, the researchers also looked at whether deaths occurred due to prostate cancer or some other cause, whether the prostate cancer spread, and several other outcomes.  Study results were further analyzed on the basis of whether patients had low-risk or intermediate-risk disease. Risk was assessed using several parameters, including Gleason score (the grade of the tumor assigned by a pathologist based on an analysis of tissue samples from a biopsy), PSA level, and clinical stage of disease. Intermediate-risk men had higher Gleason, PSA, and clinical stage values than low-risk men.

The researchers reported a statistically significant improvement in the overall survival after 10 years on the trial for participants who received the short-term ADT and radiation compared with those who received radiation therapy alone (62 percent vs. 57 percent overall survival). Radiation therapy plus short-term ADT was also associated with fewer prostate cancer-related deaths compared to radiation therapy-alone (8 percent vs. 4 percent for the entire study population).

“This study has important significance for clinical care,” says the lead author Christopher U. Jones, MD, Radiological Associates of Sacramento, Calif. “We now have strong scientific evidence about which patients with early-stage prostate cancer benefit from short-term ADT. This is important both for improved clinical care and the utilization of health care resources.”

Prostate cancer rates are higher among black men than other racial/ethnic groups. Therefore, this trial recruited nearly 400 African-American men, allowing evaluation by racial subgroups.  Similar benefits from short-term ADT were seen in white and African-American populations for 10-year overall survival, disease-specific mortality, and climbing PSA levels after initially lowered levels due to ADT.  The strong minority representation in this study will permit additional in-depth analyses of the effects of these therapies in different populations in the future.

Among men with low-risk disease, short-term ADT produced little improvement in 10-year overall or disease-specific survival. It is possible that, for patients with low-risk disease, longer follow-up is required to reveal a benefit. However, given that short-term ADT has substantial quality of life consequences, including hot flashes and higher rates of erectile dysfunction, and the 10-year disease-specific mortality in the radiation-alone arm for men with low-risk disease was 1 percent, the researchers noted that these findings do not support adding short-term ADT for low-risk prostate cancer. Newer high-dose radiation treatments may also lessen the need for use of ADT in low-risk patients.

“This type of trial is the gold standard for proving one therapy, or combination of therapies, is more effective than another, and NCI is strongly committed to sponsoring and conducting even more of these types of trials in the future,” said Jeff Abrams, MD associate director of NCI’s Cancer Therapy Evaluation Program.  “Enrolling enough patients in clinical trials is always a challenge, and we owe a great deal of gratitude to the men who participated in this trial because these results will bring benefits to many men facing prostate cancer.”

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Stem Cell Treatment May Restore Cognitive Function in Patients with Brain Cancer

July 13 2011

PHILADELPHIA — Stem cell therapy may restore cognition in patients with brain cancer who experience functional learning and memory loss often associated with radiation treatment, according to a laboratory study published in Cancer Research, a journal of the American Association for Cancer Research.

Charles Limoli, PhD, a professor in the department of radiation oncology at the University of California, Irvine, said radiation therapy is the standard of care for most brain cancers, but the side effects can be devastating.

“In almost every instance, people experience severe cognitive impairment that is progressive, debilitating and adversely impacts quality of life,” he said. “Pediatric cancer patients can experience a drop of up to three IQ points per year.”

In the current study, Limoli and colleagues subjected rats to cranial irradiation and followed up two days later with human neural stem cell transplants. A significant proportion of these cells survived and turned into brain cells found at one- and four-month evaluations. Cognitive function significantly improved compared with control rats.

Limoli said the findings of this study were significant, and may help pave the way for a human safety trial to be conducted within a few years if appropriate funding can be secured. Neural stem cells like those used in this study do not present the same ethical questions as embryonic stem cells.

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Nearly All Patients with High-grade Bladder Cancer Do Not Receive Guideline-recommended Care

July 11 2011

A study at UCLA's Jonsson Comprehensive Cancer Center found that nearly all patients with high-grade, non-invasive bladder cancer are not receiving the guideline-recommended care that would best protect them from recurrence, a finding that researchers characterized as alarming.

In fact, out of the 4,545 bladder cancer patients included in the study, only one received the comprehensive care recommended by the American Urology Association and the National Comprehensive Cancer Network.

Receiving the recommended comprehensive care for high-grade bladder cancer is critical because it can significantly minimize the likelihood that patients will die from their cancer, said Dr. Karim Chamie, a postdoctoral fellow in urologic oncology and health services research and lead author of the study.

"We were surprised by the findings in this study, particularly in an era when many suggest that doctors over-treat patients and do too much in the name of practicing defensive medicine," Chamie said. "This study suggests quite the contrary, that we don't do enough for patients with bladder cancer. If this was a report card on bladder cancer care in America, I'd say we're earning a failing grade."

The study is published July 11, 2011 in the early online edition of CANCER, a peer-reviewed journal of the American Cancer Society.

The study then investigated the cause of poor compliance. What they found was that non-compliance knew no boundaries and that patient-level factors such as age, race, ethnicity or socioeconomic status had very little impact. Instead, non-compliance with guideline-recommended care was primarily attributed to urologists. The patients in the study were elderly, but capable of withstanding these simple measures.

"It wasn't their age, race, ZIP code or how wealthy they were. It all came down to who their doctor was," Chamie said

Dr. Mark S. Litwin, professor of urology and public health and senior author of the study, said it's not clear why physicians are not routinely following established guidelines for care.

"It is puzzling, because strong evidence supports those guidelines," Litwin said. "But this is a wake-up call to all physicians caring for patients with bladder cancer. We know definitively what constitutes high-quality care. Now we just need to make sure it happens."

Patients with primary high-grade bladder cancer, which has not yet invaded the muscle of the bladder, have a 50 to 70 percent chance of their cancer coming back in the bladder following treatment. They also have a 30 to 50 percent chance of the cancer becoming more aggressive and invading into the muscle, where it is much harder to treat. Once the cancer invades the muscle, the bladder and surrounding organs must be removed and both the quality and the quantity of the patient's life are significantly impacted, Chamie said.

Chamie said that, at diagnosis, about 75 percent of bladder patients have disease that has not invaded the muscle. So treating those patients with the guideline-recommended care to help minimize recurrences and prevent invasion of the tumor into the muscle could help a large number of patients.

The recommended medical guidelines call for injecting a cancer-killing drug directly into the bladder to minimize recurrence and progression. They also recommend an intense follow-up schedule, including the repeated use of a scope to evaluate the bladder from the inside, a procedure called cystoscopy, and a urine test that is similar to a pap smear every three months to check for abnormal cells.

Only one patient in the study, which analyzed date from Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, was given the recommended care. The study also found that nearly half of urologists treating these patients had not performed at least one cystoscopy, one urine test, and one infusion of the cancer-killing drug into the bladder.

To rectify the situation, Chamie and Litwin suggest a quality-improvement initiative and or changes to physician reimbursements. To complicate matters, despite the poor compliance rate, bladder cancer is the most expensive malignancy to treat on a per-patient level. While improving compliance with changes to physician reimbursement or a quality improvement initiative will increase healthcare costs in the short term, preventing recurrences or progression of the cancer likely will cut costs in the long term.

"We have to improve compliance and there are two ways to do that: Modify our reimbursement schedules to provide incentives to doctors to follow the guidelines, or go out and interact and educate the community urologists - who are delivering the vast majority of bladder cancer care - on the importance of providing compliant care," Chamie said. "Unlike some patients diagnosed with bladder cancer after having it spread to other sites when it's too late to treat effectively, or those with low-grade tumors that are not likely to ever be aggressive, this is a potentially curable cohort of patients. If we don't do a good enough job treating these cancers, we're going to lose these patients."

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Medicare Expands Treatment Options for Patients with Advanced Prostate Cancer

Medicare Now Covers First FDA-Approved Immunotherapy for Prostate Cancer Treatment

June 30 2011

Medicare patients with metastatic prostate cancer can get a first-of-its kind treatment just approved by the Food and Drug Administration, under a final coverage decision issued today by the Centers for Medicare & Medicaid Services (CMS).

Autologous cellular immunotherapy, known clinically as sipuleucel-T, is marketed in the United States as Provenge, for treating some forms of prostate cancer in seriously ill patients. Today’s decision is effective immediately.

Provenge activates a patient’s own immune system to defend him against prostate cancer. The treatment consists of a multi-day regimen in which the patient’s white blood cells are collected and exposed to proteins that direct the white blood cells to fight prostate cancer cells. After the patient’s cells are treated, the patient receives his own cells back into his body in order to stimulate his immune system to fight the prostate cancer. This regimen is repeated over several weeks for a total of three treatments.

“We are optimistic that innovative strategies may improve the experience of care for our beneficiaries who have cancer,” said CMS Administrator Donald M. Berwick, MD “CMS is dedicated to assuring that these patients can seek the treatments they need in accordance with their wishes.”

Prostate cancer is the most common non-skin cancer in men in the United States. The cancer forms in the prostate, a gland in the male reproductive system, which can spread to other parts of the body and threaten life. In 2009, an estimated 192,280 new cases of prostate cancer were diagnosed and an estimated 27,360 men died. According to the National Cancer Institute, prostate cancer is most commmonly a cancer of older men, with most men diagnosed after 65 and the median age at diagnosis of 72.

CMS internally initiated the national coverage determination process for Provenge for multiple reasons, including: variations in local coverage; questions about the appropriate benefit category for Provenge; and inquiries from Congress. There was no prior NCD on this technology, and local contractors were generally making case by case determinations.

CMS convened the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC), a group of nationally recognized independent medical and scientific experts, on November 17, 2010 to make recommendations about the evidence. The MEDCAC votes supported coverage of Provenge for the FDA labeled indication and did not support coverage for unlabeled uses.

Today’s coverage decision includes coverage of Provenge for the uses approved by the FDA: for treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

More information for patients and health professionals about FDA’s approved uses of Provenge is online at http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210037.htm.

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Brain Cancer Patients who are able to Exercise Live Significantly Longer than Sedentary Patients

Scientists at the Duke Cancer Institute report

June 20 2011

The finding, published online Monday in the Journal of Clinical Oncology, adds to recent research that exercise improves how cancer patients feel during and after treatments, and may also extend their lives.

"This provides some initial evidence that we need to look at the effects of exercise interventions, not only to ease symptoms but also to impact progression and survival," said Lee W. Jones, PhD, associate professor in the Duke Cancer Institute and senior author of the study.

Although the study was not designed to test whether regular exercise actually causes longer survival among brain cancer patients, it established a strong correlation that could give doctors and patients a more accurate prognosis of long-term survival.

The study enrolled 243 patients at the Preston Robert Tisch Brain Tumor Center at Duke with advanced recurrent gliomas, lethal brain malignancies that typically result in a median life expectancy of less than six months.

The patients who reported participating in regular, brisk exercise ­-- the equivalent of an energetic walk five days a week for 30 minutes -- had significantly prolonged survival, living a median 21.84 months vs. 13.03 months for the most sedentary patients.

The self-reported exercise behavior offered an important additional means of predicting survival among the glioma patients beyond other measures traditionally used for prognosis, including a six-minute walk test.

Jones said the walk test is a good way to gauge the functional capacity of people with heart failure or other cardiac or pulmonary disorders, but it may not be informative for brain cancer patients who frequently suffer dizzy spells and other neurological problems that hamper walking.

Jose Cortes, a Duke patient who has battled inoperable anaplastic astrocytoma since 2009, has been an avid proponent of the power of exercise during his treatment.

"I exercised regularly prior to my illness and I wanted to stay as active as possible," Cortes said. "But it was impossible for me to do things that I could do easily before. My first goals in physical therapy were to put on my shoes without tipping over and keep my equilibrium while walking and talking or walking and turning my head."

As he met and surpassed his early goals, he began walking for 30 minutes a day and last year joined a Zumba fitness-dance class at his local YMCA.

"I wanted to be able to exercise because it makes me feel alive again," Cortes said. He cautioned that exercise is no cure –- his cancer has responded well to chemotherapy, but he said being active helps both physically and mentally.

"Exercise is a very good way to overcome the side effects of your disease," he said. "You can feel more positive about your life even if you are in a terminal state. The most important thing is to just do it at your own pace and do your best."

The Duke study demonstrates that if doctors know about their patients' exercise regimens, they will have a better way to assess long-term outcomes.

Jones said an accurate prognosis is important to determine the overall health of patients, potential tolerance for certain types of treatment, and eligibility for clinical trials.

Jones said a major goal of his research is to discover why exercise may lead to improvements in survival following a cancer diagnosis.

"Discovering these mechanisms could provide new insights into cancer progression," Lee said.

"It could also lead to novel studies where exercise is combined with certain cancer therapies to see if both interventions together are more effective at inhibiting cancer recurrence or progression, not just minimizing the adverse side effects of the cancer therapies."

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FDA Approves Lazanda® - First Fentanyl Nasal Spray for the Management of Breakthrough Pain in Cancer Patients

June 30 2011

U.S. Inc., announced that the U.S. Food and Drug Administration (FDA) has approved Lazanda® (fentanyl) nasal spray for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Lazanda marks the first FDA product approval for Archimedes Pharma. Lazanda is marketed as PecFent® (fentanyl pectin nasal spray) in Europe, where it is presently available in five countries.

“Lazanda is an important new option for patients with cancer who experience excruciating breakthrough pain," says Jeffrey H. Buchalter, chief executive officer of Archimedes Pharma. "Lazanda, which uses our patented PecSys® drug delivery system, is designed to deliver medicine in a rapid, but controlled manner, and provides patients with an effective alternative to manage their breakthrough pain.”

Breakthrough pain in cancer (BTPc) is an intense, sudden pain that is often unpredictable and debilitating and occurs despite otherwise appropriate opioid therapy for background pain. BTPc has a different profile from background pain. BTPc often has high intensity, a rapid onset, usually reaching maximum intensity within five minutes, and a short duration, lasting between 30 and 60 minutes per episode. On average, BTPc affects more than half of patients with cancer and often interferes with patients’ health and ability to engage in daily living activities.

“As the first fentanyl nasal spray in the U.S., Lazanda provides a new approach to managing the often debilitating and inadequately-treated episodes of breakthrough pain that many patients with cancer experience,” said Donald Taylor, MD, director at Taylor Research LLC., and clinical investigator for Lazanda. “Current treatment options typically utilize short-acting oral opioid medications that cannot provide pain relief with an onset of action or duration of effect that matches the time course of a BTPc episode. Lazanda’s rapid and controlled availability is a much better match for the nature of an episode of breakthrough pain, giving physicians a new and powerful tool for treating cancer breakthrough pain.”

Lazanda will be available in the second half of this year through a Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to minimize the risk of misuse, abuse, addiction, overdose, and serious complications due to medication errors. Under the Lazanda® REMS program, pharmacies, distributors, and health care professionals who prescribe to outpatients are required to enroll in the program to dispense, distribute, and prescribe Lazanda.

“We fully support the FDA mandate to implement a REMS program for Lazanda as an important way to provide patients, healthcare providers, and pharmacists with the information they need about the appropriate and safe use of Lazanda,” said Buchalter. “Archimedes Pharma looks forward to working closely with health care professionals to ensure safe and consistent access to Lazanda for the patients who are seeking relief from unbearable episodes of breakthrough pain in cancer.”

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EURTAC Phase III Study: Erlotinib Nearly Doubles Progression-Free Survival vs. Chemotherapy

July 04 2011

In the first phase III study to include Western lung cancer patients, first-line treatment with erlotinib (Tarceva) nearly doubled progression-free survival compared with chemotherapy, according to research presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC).

Erlotinib is a tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR). Non-small cell lung cancer (NSCLC) patients with EGFR activating mutations tend to respond well to TKI therapy.

"Although a growing body of evidence has been emerging about this type of lung cancer, almost all of the studies have been conducted in Asian patients, a group that historically has had significantly different results to NSCLC therapy compared to Western populations," said principal investigator Dr. Radj Gervais, MD, of the Centre François Baclesse in Caen, France. "EURTAC is the first Phase III study with first-line erlotinib in Western patients with this genetically distinct type of advanced NSCLC."

Researchers tested more than 1,000 patients over a five-year-period to find the study population of 174 patients, which were randomly assigned to receive erlotinib or platinum-based chemotherapy.

The response rate to erlotinib was 54.5%, compared with 10.5% to chemotherapy, according to preliminary results. Progression-free survival in the erlotinib arm was 9.4 months, compared with 5.2 months in the chemotherapy arm. Median survival was 22.9 months in the erlotinib arm and 18.8 months in the chemotherapy arm.

"Our results showed that first-line erlotinib nearly doubled progression-free survival; that’s a significant improvement over chemotherapy, with a better tolerability profile," Dr. Gervais said. "We now have results for the use of first-line erlotinib in Asian and Western EGFR mutation-positive patients with NSCLC, and so we can carry this knowledge into our daily practice. I think EURTAC really is a big step towards individualized lung cancer care."

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Chemotherapy and Radiation Therapy for Lung Cancer Linked to Cardiac Disorders

June 30 2011

Chemotherapy, radiation therapy, and the combination of chemotherapy and radiation therapy have been shown to result in increased survival time of patients with non-small-cell lung cancer (NSCLC). Since chemotherapy may affect healthy cells as well as cancer cells and radiation therapy in high doses can compromise the heart, a research team from the University of Texas sought to investigate the likelihood of an increased risk of developing cardiac disorders following the administration of these forms of therapy in NSCLC patients. They found that all three modalities of treatment—chemotherapy only, radiation therapy only, and chemoradiation—were associated with increased risks for developing cardiac dysfunction. Persons at highest risk were men, blacks, older patients, those with more coexisting illness, and those with advanced disease.

Patients who received chemotherapy only were more likely to develop ischemic heart disease and heart failure, while those who received chemoradiation were at increased risk for conduction disorders and heart failure. The study also found an increased risk of ischemic heart disease in patients with left-sided tumors treated with radiation only and with chemoradiation given to both lungs. The risk for cardiac dysfunction following chemoradiation was above that for chemotherapy only and radiation therapy only.

The researchers used the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare linked data files to gather information about incident cancer cases and cancer-directed therapy. The final study sample consisted of 34,209 patients aged 65 and over with stages I-IV NSCLC who were diagnosed from 1991 to 2002. The study was supported by the Agency for Healthcare Research and Quality (HS16743).

See "Cardiac toxicity in association with chemotherapy and radiation therapy in a large cohort of older patients with non-small-cell lung cancer," by Dale Hardy, PhD, Chih-Chin Liu, MS, Janice N. Cormier, MD, MPH, and others in the Annals of Oncology 21, pp. 1825-1833, 2010.

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Childhood Cancer Survivors are at High Risk for Multiple Tumors as They Age

Findings from the Childhood Cancer Survivor Study led by St. Jude Children’s Research Hospital investigators identify new cancer risks when survivors become adults; underscore the importance of regular cancer screenings

June 27 2011

The largest study yet of adult childhood cancer survivors found that the first cancer is just the beginning of a lifelong battle against different forms of the disease for about 10 percent of these survivors.

The research involved 14,358 individuals enrolled in the federally funded Childhood Cancer Survivor Study (CCSS). St. Jude Children’s Research Hospital investigators leading the effort reported that 1,382, or 9.6 percent, of survivors developed new tumors unrelated to their original cancers. About 30 percent of those survivors, 386 individuals, developed third tumors. Four or more tumors were found in 153 survivors in this study. The results appear in the June 27 online edition of the Journal of Clinical Oncology.

“These findings show that when you describe adult survivors of childhood cancer it is not sufficient to describe their risk of a first subsequent cancer, but to acknowledge that some of these patients are at risk for multiple cancers. This is the first study to more fully enumerate that risk,” said Gregory Armstrong, MD, the study’s principal investigator and an assistant member of the St. Jude Department of Epidemiology and Cancer Control.

The work underscores the importance of cancer screenings for this growing population. “Too often, survivors still are not getting these important cancer screening tests beginning as early or as often as recommended,” Armstrong said. For example, mammograms beginning at age 25 rather than age 40 are recommended for female survivors whose childhood treatment included chest radiation of 20 grays or more. A gray is a measure of absorbed radiation.

An estimated 366,000 Americans alive today are childhood cancer survivors. With overall long-term childhood cancer survival rates now at 80 percent, the ranks of survivors are expected to keep growing. The CCSS was launched in 1994 to identify the challenges facing childhood cancer survivors and to develop new methods to ease or prevent late effects. St. Jude is the study’s central coordinating institution. St. Jude scientists are also focused on using genomics and other tools to develop the next generation of cancer therapies and better match patients with existing therapy to increase cures but decrease the risk of treatment-related toxicities, including second cancers.

In this study, half of the participants had survived at least 23 years since their childhood cancers were found. Their median age was 32 years old, meaning most had yet to reach the age when rates of prostate, breast and other cancers increase sharply in the general population.

Almost 70 percent of study participants received radiation as part of their successful childhood cancer treatment. This study reinforced earlier research that linked radiation therapy with an increased risk of developing additional tumors, malignant and benign, later in life. Female survivors whose childhood cancer treatment included radiation were among those at highest risk for later tumors, particularly breast tumors.

For 735 survivors, the second tumors were malignant and thus life-threatening.

Risks were also associated with benign tumors. Investigators showed survivors whose second tumor was a non-melanoma skin cancer had a 1 in 5 chance of being diagnosed with another, more aggressive cancer within 15 years. The group included 485 survivors with either basal or squamous cell skin cancers. “These survivors are candidates for additional genetic evaluation to look for an underlying genetic propensity for tumor development or an inability to protect healthy cells against the harmful effects of radiation,” Armstrong said.

Of the 176 survivors whose second tumors were found in the breast, 42 women developed multiple tumors. For many, researchers reported that the tumors apparently developed independently in both breasts almost simultaneously. “This finding reinforces previous reports of multiple breast cancers and defines them as a significant risk,” Armstrong said.

This study included survivors whose cancers were found between 1970 and 1986 when they were age 20 or younger. Participants were treated at one of 26 institutions in the United States or Canada and survived at least five years after their cancer diagnosis.

The other authors were Wei Liu, Deokuma Srivastava and senior author Les Robison, all of St. Jude; Wendy Leisenring, Fred Hutchison Cancer Research Center; Yutaka Yasui, University of Alberta; Sue Hammond, The Ohio State University; Smita Bhatia, City of Hope; Joseph Neglia, University of Minnesota Medical School; and Marilyn Stovall, University of Texas MD Anderson Cancer Center.

The National Cancer Institute and ALSAC funded this research.

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FDA Povides Updated Safety Data Silicone Gel-Filled Breast Implants

Agency highlights information women should know when considering implants

June 22 2011

The U.S. Food and Drug Administration released a report today updating the clinical and scientific information for silicone gel-filled breast implants, including preliminary safety data from studies conducted by the manufacturers as a condition of their November 2006 approval.

While the report confirms that silicone gel-filled breast implants are safe and effective when used as intended, women should fully understand the risks prior to considering silicone gel-filled breast implants for breast augmentation or reconstruction.

Based on the report, women should know:

• Breast implants are not lifetime devices. The longer a woman has silicone gel-filled breast implants, the more likely she is to experience complications. One in 5 patients who received implants for breast augmentation will need them removed within 10 years of implantation. For patients who received implants for breast reconstruction, as many as 1 in 2 will require removal 10 years after implantation.
• The most frequently observed complications and outcomes are capsular contracture (hardening of the area around the implant), reoperation (additional surgeries) and implant removal. Other common complications include implant rupture, wrinkling, asymmetry, scarring, pain, and infection.
• The complications that existed for women receiving breast implants at the time of approval are similar to the complications observed today.
• Preliminary data do not indicate that silicone gel-filled breast implants cause breast cancer, reproductive problems or connective tissue disease, such as rheumatoid arthritis. However, in order to rule out these and other rare complications, studies would need to enroll more women and be longer than those conducted thus far.

The report includes preliminary safety data from post-approval studies conducted by each of the two breast implant manufacturers (Allergan and Mentor), a summary and analysis of adverse events received over the years by the FDA, and a comprehensive review and analysis of recent scientific publications that discuss the safety and effectiveness of silicone gel-filled breast implants. FDA approved silicone gel-filled breast implants in November 2006 for breast augmentation in women over age 22 and for breast reconstruction in all women.

As a condition of approval, the FDA required each of the two companies to conduct six post-approval studies to characterize the long-term performance and safety of the devices.

Both manufacturers have communicated to the FDA the difficulties in following women who have received silicone gel-filled breast implants. The FDA is working with Allergan and Mentor to address those challenges and increase patient participation and follow-up.

“The FDA will continue to monitor and collect safety and performance information on silicone gel-filled breast implants, but it is important that women with breast implants see their health care providers if they experience any symptoms,” Jeffrey Shuren, MD, JD, director of FDA’s Center for Devices and Radiological Health. “Women who have enrolled in studies should continue to participate so that we may better understand the long-term performance of these implants and identify any potential problems.”

The FDA is holding an expert advisory panel in the next few months to discuss how post-approval studies on breast implants can be more effective.

At this time, the FDA is recommending that health care professionals and women who have silicone gel-filled breast implants do the following:

• Follow up. Women should continue to routinely follow up with their health care professionals. This includes getting routine MRIs to detect silent rupture.
• Be aware. Breast implants are not lifetime devices. Breast implants are associated with significant local complications and outcomes, including capsular contracture, reoperation, removal, and implant rupture. Some women also experience breast pain, wrinkling, asymmetry, scarring and infection.
• Pay attention to changes. Women should notify their health care professionals if they develop any unusual symptoms. All serious side effects should be reported to the breast implant manufacturer and Medwatch, the FDA’s safety information and adverse event reporting program. Report online1 or by calling 800-332-1088.
• Stay in touch. If a woman has enrolled in a manufacturer-sponsored post-approval study, she should continue to participate. These studies are the best way to collect information about the long-term rates of complications.

The report is part of the FDA’s ongoing effort to ensure that women who have or who may be considering silicone gel-filled breast implants are informed of all possible complications and outcomes. As an additional step, the agency has redesigned its website2 to include comprehensive information on silicone gel-filled and saline-filled breast implants.

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Abbott Receives FDA Approval for a New Six-Month Formulation of Lupron Depot®

for the Palliative Treatment of Advanced Prostate Cancer

June 20 2011

Abbott Park, Illinois — Abbott announced today that the U.S. Food and Drug Administration (FDA) has approved a new 45 mg for six-month administration formulation of Lupron Depot® (leuprolide acetate for depot suspension), a medication used for the palliative treatment of advanced prostate cancer.

"Lupron Depot is an important treatment option for many patients with advanced prostate cancer," said Eugene Sun, MD, vice president, Global Pharmaceutical Development, Abbott. "Approval of a new six-month formulation means that physicians and patients who have chosen Lupron Depot now have an additional treatment option."

Patients with advanced prostate cancer who have been prescribed Lupron Depot receive an injection that is administered in the physician office. The three current formulations of Lupron Depot have allowed patients to receive their treatment every month, every three months or every four months. Now, patients who are prescribed the newly approved formulation may receive their treatments every six months, providing additional dosing flexibility for patients with advanced prostate cancer.

Lupron Depot works by suppressing the production of the hormone testosterone. This decrease in testosterone can help slow or stop the growth of hormone-dependent cancer cells, and may relieve pain and other symptoms related to advanced prostate cancer.

Abbott's submission to the FDA was supported by new data from a 48-week, open-label study involving 151 patients with prostate cancer. Patients received a total of two injections, 24 weeks apart, and were followed for nearly one year to evaluate testosterone suppression and safety. Overall, testosterone suppression with this new 45 mg six-month depot formulation was sustained in patients throughout the treatment period. The onset of testosterone suppression was consistent with other currently available Lupron Depot formulations. The most common side effects from this 48-week study were flushing, injection site pain, respiratory infection and fatigue. The 45 mg for six-month administration formulation is expected to be available in late June.

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Cancer Support Community Introduces First-of-its-Kind, Free Mobile App

CancerSupportSource™ Uniquely Addresses the Social and Emotional Needs of Those Living with Cancer  

June 14 2011

WASHINGTON, D.C. – The Cancer Support Community (CSC - www.cancersupportcommunity.org) -- an international non-profit dedicated to providing support, education and hope to people impacted by cancer -- today announced a free new service: CancerSupportSource™, an innovative mobile application providing cancer patients and their caregivers with a unique set of tools addressing their physical, social and emotional concerns related to living with cancer and its treatment. The app is available for download via the iTunes Store (category: Medical).    

By employing CancerSupportSource™, users can monitor their concerns over time; record thoughts and questions in a personal journal; access educational information and a community support network; and report progress to their health care team. Developed with support from Genentech, CancerSupportSource™ is available at no cost and is designed for use with the iPhonet™ and iPod Touch™.

  A critical element of CancerSupportSource™ is that it enables users to forge connections with those who are coping with similar issues. “This can be intrinsically healing and is a part of care and wellness management that is often overlooked,” says Kim Thiboldeaux, president and CEO of the Cancer Support Community.  “We want users to know that they don’t have to face cancer alone – there is a whole community of support behind them.” To aid this endeavor, the app allows the user to find a nearby CSC affiliate, join the organization’s Online Community and access a variety of CSC’s free support services. In addition, CancerSupportSource™ allows users to:

• Monitor common concerns such as fatigue, difficulty sleeping, sadness, anxiety and pain
• Track potential life worries, such as family, work, money and nutrition
• Record thoughts and questions in a personal journal

“The beauty of the CancerSupportSource™ is that users can access it anytime, anywhere,” says Thiboldeaux. “It’s available 24/7, 365 days a year.”

Beta-Testing Phase Yields Useful Results
CancerSupportSource™ was beta-tested over the past six months and is now utilized by more than 550 people in 40 countries.  “Trends in mobile technology indicate that the logical first step in introducing a new application is to build a groundswell of support,” says Thiboldeaux. The beta-testing phase allowed CSC to gather valuable usability information and connect with specific users for feedback. “This test period has allowed us to refine the app so that it truly meets the psychosocial needs of people managing a cancer diagnosis,” she reports.

The initial feedback is positive. “CancerSupportSource™ keeps me going in between the online support group I attend weekly through CSC’s Online Community,” says Ellen Dominguez, a nine-year ovarian cancer survivor.

Karin Diamond, currently battling Hodgkin’s lymphoma, adds, “Overall, what I like most about the app is that it provides data and reference points for the user on side effects that are not given nearly enough attention.  Whether it’s an effect of chemo brain or the whirlwind of doctor appointments, treatment and blood work schedules, days can tend to meld into each other and symptoms and side effects are easily forgotten.  I find myself using the app to create bullet points of  medical issues to discuss.  I love the fact that the support, reference material and the tracking of your own symptoms are right there at your fingertips.”

Cancer Support Community’s Use of Technology
According to a February 2011 survey by Cisco, a leading communications technology and services company, global mobile data traffic nearly tripled in 2010 and is expected to increase 26-fold between 2010 and 2015.  Mobile data, cites the report, is well on its way to becoming a necessity. Says Thiboldeaux, “With the introduction of CancerSupportSource™, CSC continues to showcase its effective use of new technologies to communicate with and provide vital information to all people impacted by cancer.”   This is not new for the organization.   CSC has long been a pioneer in the use of technology to support and educate people affected by cancer.  The largest provider of professionally-facilitated, real-time and online cancer support groups, the organization has been offering these groups since 2002. 

About the Cancer Support Community
Backed by evidence that the best cancer care includes emotional and social support, the Cancer Support Community offers these services to all people affected by cancer.  Likely the largest professionally-led network of cancer support worldwide, the organization delivers a comprehensive menu of personalized and essential services.  Because no cancer care plan is complete without emotional and social support, the Cancer Support Community has a vibrant network of community-based centers and online services run by trained and licensed professionals.  

In July 2009, The Wellness Community and Gilda’s Club Worldwide joined forces to become the Cancer Support Community.  The combined organization provides high-quality psychological and social support through a network of nearly 50 local affiliates, more than 100 satellite locations and online.  For more information, visit www.cancersupportcommunity.org.

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FDA Approves New Test to Help Determine if Breast Cancer Patients are Candidates for Herceptin Treatment

June 14 2011

The U.S. Food and Drug Administration today approved a new genetic test that will help health care professionals determine if women with breast cancer are HER2-positive and, therefore, candidates for Herceptin (trastuzumab), a commonly used breast cancer treatment.

The test, called Inform Dual ISH, allows for measurement of the number of copies of the HER2 gene in tumor tissue. The HER2 gene is located on chromosome 17 in human cells. An excessive amount of the protein produced by the gene is found in some types of cancer cells, including breast cancer cells.

The Inform Dual ISH test allows lab personnel to count the number of copies of HER2 genes on chromosome 17 in a small sample of the breast tumor. The sample is stained with chemicals that cause copies of HER2 genes and chromosome 17 to change color. Copies of the HER2 gene appear black and copies of chromosome 17 appear red. These color changes can be seen under a standard microscope.

This feature allows lab personnel to see and count copies of chromosome 17 and HER2 genes on the same slide, similar to HER2 amplification measurements that have traditionally only been available using fluorescence microscopes. The Inform Dual ISH, however, allows lab staff to see the HER2 and chromosome 17 signals directly under a microscope, for longer periods of time.

"When used with other clinical information and laboratory tests, this test can provide health care professionals with additional insight on treatment decisions for patients with breast cancer," said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health.

The FDA based its approval of the Inform Dual ISH on a U.S. study involving tumor samples from 510 patients with breast cancer. This study showed that the test was effective in confirming that a patient’s tumor sample contained more than the normal number of copies of the HER2 gene in 96 percent of the HER2 positive tumor samples. Patients with more than the normal number of copies of the HER2 gene are considered candidates for Herceptin therapy.

The study also showed that the test was effective at excluding the possibility that more than the normal number of copies of the HER2 gene were present in 92.3 percent of the HER2 negative tumor samples. Patients who do not have more than the normal number of copies of the HER2 gene are typically not candidates for Herceptin therapy. The ability to identify patients who are HER2-positive is a useful tool for physicians who may be considering treatment with Herceptin for their breast cancer patients.

Breast cancer is the second leading cause of cancer-related death among women. An estimated 207,090 new cases of breast cancer were diagnosed in the United States during 2010 and about 39,840 women died from the disease, according to the National Cancer Institute. About 20 percent of women diagnosed with breast cancer are HER2-positive.

Tuscon, Ariz.-based Ventana Medical Systems manufactures the Inform Dual ISH test. Herceptin is marketed by South San Francisco based-Genentech, a member of the Roche Group.

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Certain Head and Neck Cancer Patients Benefit from Second Round of Treatment

June 13 2011

A new study has determined predictors that can better identify patients who will benefit from a potentially toxic second course of treatment, which offers a small but real chance of cure in select patients with head and neck cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings could help guide treatment decisions for head and neck cancer patients.

Radiation is often used to treat patients with head and neck cancer. If their cancer reappears, they have limited treatment choices: chemotherapy is not curative, and surgery can be curative but is often not possible. Chemotherapy and a second course of radiation have previously been shown to be another option. Joseph Salama, MD, formerly of the University of Chicago, and his colleagues conducted an analysis of prior studies to determine how patients tolerate this second round of treatment and which patients benefit the most from it.

The investigators analyzed data from 166 patients with head and neck cancer who received a first round of radiation followed by a second round plus chemotherapy because their cancer recurred or they developed a new tumor. The second course of treatment could cure approximately 25 percent of patients at two years, but it was quite toxic. (Some patients lost the ability to speak or swallow. In addition, approximately 20 percent of patients died from treatment-related complications.)

Certain patients benefited from the treatment over others. Those who were cancer-free for a longer period of time, did not have chemotherapy with their first course of radiation, were treated with a higher dose of radiation in the second round, and had surgery prior to the second course of radiation were more likely to be cured at two years than those who had none or only one of these features. “These can help doctors determine which patients are best suited for a second course of radiation with chemotherapy for head and neck cancer,” said Dr. Salama.

The authors concluded that for patients with recurrent head and neck cancer in a previously irradiated area, concomitant chemotherapy with reirradiation is a treatment option that offers a small but real chance of cure in select patients; however, due to the risk of severe toxicity, the treatment should be limited to investigational studies and experienced medical centers.

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Access to Personal Medical Records Increases Satisfaction Among New Cancer Patients

May 23 2011

A new analysis has found that allowing full access to personal medical records increases satisfaction without increasing anxiety in newly diagnosed cancer patients. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that providing accurate information to patients through medical records can be a beneficial complement to verbal communication with their physicians.

Most cancer patients say they are eager to receive comprehensive information about their disease, but many physicians believe that providing it increases anxiety and may be deleterious for patients. To clarify the issue, Gwenaelle Gravis, MD, of the Paoli-Calmettes Institute in Marseille, France, and her colleagues compared two types of information delivery on cancer patients’ anxiety, quality of life, and satisfaction: providing systematic full access to an organized medical record (OMR) versus “on request information.”

The randomized study included 350 patients who were recently diagnosed with breast, colon cancer, or lymphoma, and who were treated with chemotherapy at the Paoli-Calmettes Institute’s Regional Comprehensive Cancer Center. Patients who had the opportunity to accept an OMR could receive a briefcase (that the patient was advised to bring to each visit so that it could be updated) that included administrative information and reports on surgery, pathology, hospitalizations, nurse narratives, radiology, and biology as well as overall information concerning the patient’s treatment. Patients also received a medical lexicon and a user guide, plus help from medical staff to understand the various documents. Most patients (98 percent) who had the opportunity to obtain an OMR chose to do so. Patients who received “on request information” were provided with information and medical records only at the physician’s initiative or upon the patient’s request.

After exclusions for various reasons, 295 patients were analyzed. Anxiety levels and quality of life scores were similar in both groups during the study; however patients with OMR access were 1.68 times more likely to be satisfied with information and were 1.86 times more likely to feel fully informed.

The investigators found that 70.4 percent of the patients who received an OMR said that in hindsight they would choose again to receive it, and 74.8 percent did not regret their choice. The majority of patients declared that the OMR had not been a source of anxiety for them, that they understood the information enclosed, and that they did not discover any unwanted information. Most patients also said that the OMR allowed them to understand their disease more thoroughly and that it helped them discuss their condition with their relatives and physicians.

“Information is crucial to make decisions regarding treatment options and, for the patient and his family, to better cope with the disease and its implications,” said Dr. Gravis. “Having full access to his own medical record with the possibility to consult it only if desired increases the patient’s trust in the physician and medical team,” she added.

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FDA Approves Sutent for Rare Type of Pancreatic Cancer

May 20 2011

The U.S. Food and Drug Administration today approved Sutent (sunitinib) to treat patients with progressive neuroendocrine cancerous tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body (metastatic).

Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.

This is the second new approval by the FDA to treat patients with this disease; on May 5, the agency approved Afinitor (everolimus).

“FDA believes it is important to provide cancer patients with as many treatment options as possible,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “The agency is committed to working with companies to bring innovative new therapies to the market and encourages companies to continue exploring additional uses for approved products.”

The safety and effectiveness of Sutent was established in a single study of 171 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease who received Sutent or a placebo (sugar pill). The study was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).

Results from the study demonstrate that Sutent provided benefit to patients by prolonging the median length of time they lived without the cancer spreading or worsening to 10.2 months compared to 5.4 months for patients who received placebo.

In patients treated with Sutent for neuroendocrine pancreatic tumors, the most commonly reported side effects included diarrhea, nausea, vomiting, fatigue, anorexia, high blood pressure, energy loss (asthenia), stomach (abdominal) pain, changes in hair color, inflammation of the mouth (stomatitis), and a decrease in infection-fighting white blood cells (neutropenia).

Sutent is also FDA-approved to treat patients with late-stage kidney cancer (metastatic renal cell carcinoma) and to treat patients with GIST (gastrointestinal stromal tumor), a rare cancer of the stomach, bowel, or esophagus.

Sutent is marketed by New York City-based Pfizer.

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ASCO Launches Cancer.Net Mobile, a New App for iPhone, iPad, and iPod Touch that Puts Cancer Care in the Hands of Patients and Caregivers

May 02 2011

ALEXANDRIA, VA – The American Society of Clinical Oncology (ASCO), the world’s leading professional organization representing cancer physicians, today released Cancer.Net Mobile for the iPhone, iPad, and iPod Touch – a free app designed by oncologists to help people with cancer and their caregivers plan and manage cancer treatment and care. The app includes comprehensive, doctor-approved information on more than 120 cancer types, together with a package of interactive tools for patients. Cancer.Net Mobile is available for download in Apple’s App Store and is the mobile companion to ASCO’s award-winning Cancer.Net website (www.Cancer.Net).

“Cancer.Net Mobile puts up-to-date, accurate cancer information and interactive tools at the fingertips of people living with cancer and their families and caregivers, wherever they are,” said ASCO CEO Allen S. Lichter, MD. “Cancer.Net Mobile was developed by leading cancer doctors with patients and their caregivers in mind, to help them take charge of their cancer care and get the most out of doctor’s visits.”

In addition to its comprehensive cancer guides covering more than 120 common and rare types of cancer, Cancer.Net Mobile includes interactive tools for patients and caregivers to:

• Keep track of questions to ask their doctors, record voice answers, and choose from frequently-asked questions suggested by Cancer.Net experts
• Save important information about prescribed medications, including photos of medicine labels and bottles (on camera-enabled devices)
• Track the time and severity of symptoms and side effects during treatment, to aid in reporting them during doctor’s visits
• Learn about new cancer care topics through weekly podcast and video interviews with ASCO member physicians

Cancer.Net Mobile offers a portable version of the extensive cancer information library available on the Cancer.Net website, with expert information about treating cancer, managing side effects, managing the cost of care, and coping with a cancer diagnosis. All Cancer.Net content is reviewed for accuracy and completeness by an editorial board composed of more than 150 medical, surgical, radiation, and pediatric oncologists; oncology nurses; social workers; and patient advocates. This ensures that the cancer information provided reflects the latest advances in cancer science and clinical practice. Cancer.Net is supported by the Conquer Cancer Foundation of ASCO.

Cancer.Net Mobile is available for download in Apple’s App Store at http://itunes.com/apps/cancernetmobile (iTunes required). It is compatible with iPhone, iPad, and iPod Touch devices running iOS version 3.2 or later. Cancer.Net Mobile is a free tool provided by ASCO. Cancer.Net Mobile app updates will be issued regularly as the cancer guide content is updated.

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DNA Repair System Affects Colon Cancer Recurrence and Survival

May 20 2011

Colorectal cancer patients with defects in mismatch repair—one of the body’s systems for repairing DNA damage--have lower recurrence rates and better survival rates than patients without such defects, according to a study published online May 19th in the Journal of the National Cancer Institute.

About 15% of colorectal cancers are associated with mismatch repair defects. Some defects are caused by the inherited gene mutations found in Lynch syndrome and others occur by chance, or “sporadically.” But it has never been clear whether mismatch repair defects are linked to cancer recurrence rates, time-to-recurrence and site of recurrence and whether such defects influence response to chemotherapy.

To explore these questions, Frank A. Sinicrope, MD, of the Mayo Clinic in Rochester, Minn., and colleagues analyzed data from more than 2,000 clinical trial patients who had been treated after surgery with chemotherapy that included 5-fluorouracil (5-FU), a standard drug used in colorectal cancer. All patients had stage II or III colon cancer.

The patients with defective mismatch repair had lower rates of tumor recurrence, longer remissions, fewer metastases, and better survival rates compared to those without the defects. Both overall survival and disease-free survival were improved.

Whether mismatch repair status influences response to 5-FU therapy has been a subject of some debate.  In this study treatment with 5-FU reduced recurrence rates in stage III, regardless of mismatch repair status, but not stage II patients.

The researchers also compared the effects of 5-FU-based therapy in patients thought to have inherited mismatch repair defects versus those whose defects occurred sporadically.  They suggest that 5-FU appeared to reduce recurrences only in those with inherited defects.

“In conclusion,” they write, “our data demonstrate that patients with defective mismatch repair colon cancers have a statistically significant reduction in their rates of tumor recurrence, a delayed time to recurrence, and better survival rates” than those without the defects. They note that the difference between inherited and sporadic tumors, though a preliminary finding, warrants further study.

In an accompanying editorial, Sabine Tejpar, MD, PhD, of University Hospital Gasthuisberg, Leuven, Belgium, and colleagues note that the influence of mismatch repair defects on patients’ prognosis and response to 5-FU has long been a contentious issue. They say that this study, with its large number of samples, provides “valuable information about the prognostic and certainly the predictive role” of mismatch repair defects.    The editorialists conclude that it will be important to validate whether patients should have their mismatch repair defects identified as hereditary or sporadic before deciding on chemotherapy with 5-FU.

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National Cancer Survivors Day® is Sunday, June 5, 2011

May 20 2011

FRANKLIN, TN – America's 12 million cancer survivors will join survivors around the world in observing the 24th annual National Cancer Survivors Day® on Sunday, June 5, 2011. Hundreds of communities worldwide will host events on this day to celebrate life and demonstrate that life after a cancer diagnosis can be meaningful and productive.

National Cancer Survivors Day is a treasured annual celebration of life. Joy and hope, camaraderie and faith, and triumph over adversity will be on full display. It is a day for everyone, whether you're a cancer survivor, a family member, a friend, or a medical professional. This day provides an opportunity for cancer survivors to connect with other survivors, and recognize the healthcare providers, families, and friends who have supported them along the way. NCSD activities will be as diversified as the towns and cities where the events are held and will include parades, carnivals, races, art exhibits, ball games, contest, dances, inspirational programs and more.

The National Cancer Survivors Day Foundation, administrator for the celebration, is encouraging everyone to participate in their community’s event. To locate the one nearest you, check with your local cancer treatment center, hospital, or American Cancer Society office. You can also download a free planning guide at planning guide at ncsd.org if you’re interested in hosting an event. “Come join in the fun and see for yourself that life can go on, and is sometimes even enhanced by a cancer diagnosis,” says Foundation spokesperson, Paula Chadwell.

NCSD started in the United States and is now worldwide, says Chadwell, and it is observed in countries as far away as Australia, Greece, Italy, Malaysia, and Saudi Arabia.

The non-profit National Cancer Survivors Day Foundation supports hundreds of hospitals, support groups, and other cancer-related organizations that host National Cancer Survivors Day events in their communities, by providing free guidance, education and networking. Its primary mission is to educate the public on the issues of cancer survivorship in order to better the quality of life for cancer survivors.

“A ‘survivor’ is anyone living with a history of cancer – from the moment of diagnosis through the remainder of life,” as defined by the Foundation. Cancer survivors may face many challenges such as hindered access to cancer specialists and promising new treatments, inadequate or no insurance, financial hardships, employment problems, and psychological struggles. “Despite these difficulties, cancer survivors can live active, productive lives,” says Chadwell.

The National Cancer Survivors Day Foundation, along with NCSD 2011 national sponsors Bristol-Myers Squibb, Coping® With Cancer magazine, and Lilly Oncology, is encouraging a greater commitment to resolving the issues of cancer survivorship. “More resources, research, and survivor-friendly legislation is needed to improve the quality of life of cancer survivors,” says Chadwell. “The accomplishments of modern science are evident in the ever growing cancer survivor population. Addressing the poorly understood needs of these survivors is becoming a formidable challenge.”

To find out more about National Cancer Survivors Day, visit www.ncsd.org.

About the National Sponsors
The National Sponsors for National Cancer Survivors Day 2011 are:
Bristol-Myers Squibb (www.bms.com), Coping® With Cancer, the magazine for people whose lives have been touched by cancer (www.copingmag.com), and Lilly Oncology (www.lillyoncology.com).

More information on cancer and cancer survivorship:
National Cancer Survivors Day: www.ncsd.org
National Cancer Institute: www.cancer.gov
American Society of Clinical Oncology: www.cancer.net
American Cancer Society’s Cancer Facts & Figures: http://www.cancer.org/Research/CancerFactsFigures/index
American Cancer Society: www.cancer.org

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Sacrificing a Healthy Breast: Few Regret Elective Mastectomy 20 Years Later

Survey Finds 92 Percent of Women Would Do it Again

April 29 2011

Washington - Ninety percent of breast cancer patients who elected to have a contralateral prophylactic mastectomy (removal of the second healthy breast) to minimize risk of a second cancer remained satisfied with their decision 20 years later, according to a study presented this week at the annual meeting of the American Society of Breast Surgeons (ASBrS). The research found that while many acknowledged adverse effects, the psychosocial implications of their decisions did not increase over time and 92 percent of participants would make the same choice today.

Researchers at Mayo Clinic, Rochester, Minn., surveyed women diagnosed with unilateral breast cancer who had undergone a contralateral prophylactic mastectomy in their facility between 1960 and 1993. An initial questionnaire was completed an average of 10 years after the elective mastectomy. This week, researchers reported results of a follow-up survey completed by 269 of these women an average of 20 years after their surgeries.

According to researcher Judy C. Boughey, MD, “We found remarkable stability across the two surveys on participant satisfaction. In fact, when women changed their opinions, they generally indicated greater, rather than less, comfort with their choice.”

Patients who already have had breast cancer are at slightly greater risk for a second cancer than the general population. Further, many women who chose prophylactic mastectomies have breast cancer family histories, compounding their chances of a contralateral breast cancer.

The first survey found that 86 percent of participants were satisfied 10 years after their procedures, while 90 percent indicated satisfaction after 20 years. Only six percent reported dissatisfaction with their decision, and that figure remained constant across both questionnaires. In the recent survey, 93 percent felt they made an informed decision that reflected their overall values. Almost 80 percent of these women also had breast reconstruction.

When recounting the adverse effects, patients frequently cited body appearance, sense of femininity and sexual relationships. This remained constant over time.

Patients describing the positive impact of their choice in their own words commented: “I don’t seem to worry about breast cancer now…” “By having a prophylactic mastectomy, my fears (many) were erased, not 100 percent, but close to it.” “I didn’t want to be worrying and thinking about it (cancer in the other breast)…”

Noting that prophylactic mastectomy rates have been steadily increasing, Dr. Boughey believes that knowing few women regret their decisions should help reassure those facing this difficult choice today. However, she advises all women to consider such a decision carefully and to balance the negative consequences of mastectomy with their risk of cancer recurrence and need to achieve peace-of-mind.

“Because patients in our survey showed a high degree of satisfaction doesn’t mean the choice is right for everybody,” she said. “This is a deeply personal decision. Understanding all the consequences is extremely important.”

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FDA Approves New Treatment for Rare Type of Pancreatic Cancer

May 06 2011

The U.S. Food and Drug Administration approved Afinitor (everolimus) to treat patients with progressive neuroendocrine tumors located in the pancreas (PNET) that cannot be removed by surgery or that have spread to other parts of the body (metastatic).

Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.

“Patients with this cancer have few effective treatment options,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas.”

The safety and effectiveness of Afinitor was established a clinical trial in 410 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease. Patients in the study were selected to receive Afinitor or placebo (sugar pill). The trial was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).

In patients treated with Afinitor, the median length of time they lived without the cancer spreading or worsening was 11 months compared with 4.6 months in patients who received placebo. Patients who received placebo were able to receive Afinitor if their disease worsened.

In patients treated with Afinitor for neuroendocrine pancreatic tumors, the most commonly reported side effects included inflammation of the mouth (stomatitis), rash, diarrhea, fatigue, swelling (edema), stomach (abdominal) pain, nausea, fever, and headache.

Afinitor is also approved to treat patients with kidney cancer (advanced renal cell carcinoma) after they fail treatment with Sutent (sunitinib) or Nexavar (sorafenib); and patients with subependymal giant cell astrocytoma (a type of brain cancer) associated with tuberous sclerosis (a disease that causes tumors in various parts of the body), who cannot be treated by surgery.

Afinitor has another trade name, Zortress, and is approved to treat certain adult patients to prevent organ rejection after a kidney transplant. Zortress has a different safety profile in these patients.

Afinitor is marketed by East Hanover, N.J.-based Novartis.

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New Study Shows Blood Pressure Increase Indicates Treatment Response

April 29 2011

Patients who develop high blood pressure while being treated for advanced kidney cancer with the drug sunitinib respond better to treatment, maintain longer progression-free survival, and survive longer, according to a Cleveland Clinic-led study.

The study, published today in The Journal of the National Cancer Institute, demonstrates that high blood pressure (hypertension) is a significant independent predictor of improved outcomes for patients with metastatic renal cell carcinoma.

“These findings support the hypothesis that high blood pressure may act as a biomarker of a medication’s anti-tumor effectiveness,” said Brian Rini, MD, a staff physician in Cleveland Clinic’s Taussig Cancer Institute. “What that means is that physicians may be able to monitor a patient’s blood pressure to gauge how effectively sunitinib is treating their advanced kidney cancer.”

In the retrospective study led by Dr. Rini, patients whose maximum systolic blood pressure reached 140 mmHg or greater survived nearly four times longer (30.5 months) compared to those who had lower maximum systolic pressure (7.8 months). Those whose maximum diastolic blood pressure reached 90 mmHg or greater survived twice as long (32.2 months compared to 14.9 months).

Hypertensive patients also experienced 2.5- to 5-times longer progression-free survival – the period of time during which the tumor either shrank or did not grow. Those with systolic hypertension had 12.5 months of progression-free survival compared to 2.5 months in patients without hypertension. Those with diastolic hypertension had 13.4 months of progression-free survival, compared to 5.3 months in patients without hypertension. “Most importantly, these results may give us greater insight into the biology of kidney cancer and the factors that determine a patient’s response to sunitinib and other similar drugs in order to extend the benefits to more people,” Rini said.

The majority of the 544 patients in the efficacy analysis experienced hypertension at some point during their sunitinib treatment – 81 percent had systolic hypertension (140 or higher), while 67 percent had diastolic hypertension (90 or higher).

The use of blood pressure-lowering medication did not reduce the treatment’s anti-tumor effectiveness.

Although patients with hypertension developed more kidney toxicity than patients without hypertension, hypertension-associated side effects were uncommon.

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FDA Approves Zytiga for Late-stage Prostate Cancer

April 28 2011

The U.S. Food and Drug Administration today approved Zytiga (abiraterone acetate) in combination with prednisone (a steroid) to treat patients with late-stage (metastatic) castration-resistant prostate cancer who have received prior docetaxel (chemotherapy).

In prostate cancer, the male sex hormone testosterone stimulates prostate tumors to grow. Drugs or surgery are used to reduce testosterone production or to block testosterone’s effects. However, sometimes prostate cancer can continue to grow even when testosterone levels are low. Men with these cancers are said to have castration-resistant prostate cancer.

Zytiga is a pill that targets a protein called cytochrome P450 17A1 (CYP17A1) which plays an important role in the production of testosterone. The drug works by decreasing the production of this hormone that would stimulate cancer cells to continue growing.

The application was reviewed under the FDA’s priority review program, which provides for an expedited six-month review for drugs that may offer major advances in treatment, or provide a treatment when no adequate therapy exists. Zytiga is being approved ahead of the product’s June 20, 2011 regulatory goal date.

“Zytiga prolonged the lives of men with late-stage prostate cancer who had received prior treatments and had few available therapeutic options,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

Zytiga’s safety and effectiveness were established in a clinical study of 1,195 patients with late-stage castration-resistant prostate cancer who had received prior treatment with docetaxel chemotherapy. Patients received either Zytiga once daily in combination with prednisone two times a day or a placebo (sugar pill) twice daily in combination with prednisone.

The study was designed to measure overall survival, the length of time from when the treatment started until a patient's death. Patients who received the Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination.

The most commonly reported side effects in patients receiving Zytiga included joint swelling or discomfort, low levels of potassium in the blood, fluid retention (usually of the legs and feet), muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, high blood pressure, heartbeat disorders, urinary frequency, increased nighttime urination, upset stomach or indigestion and upper respiratory tract infection.

Zytiga is marketed by Horsham, PA-based Centocor Ortho Biotech, Inc.

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ASCO Issues Provisional Clinical Opinion Recommending EGFR Mutation Testing Prior to Use of First-Line Targeted Drugs for Advanced Lung Cancer

April 11 2011

ALEXANDRIA, VA - The American Society of Clinical Oncology (ASCO) today issued a provisional clinical opinion (PCO) on the clinical use of epidermal growth factor receptor (EGFR) mutation testing to identify patients with advanced lung cancer who may benefit from targeted agents known as EGFR tyrosine kinase inhibitors. These treatments include gefitinib (Iressa) and erlotinib (Tarceva). The PCO, which is based on the results of five recent randomized clinical trials, recommends that patients with advanced non-small cell lung cancer who are being considered for first-line therapy with an EGFR tyrosine kinase inhibitor (meaning the patient has not previously been treated with chemotherapy or other anti-cancer drugs) should first have their tumor tested for EGFR mutations. Such testing is currently available, both at academic medical centers and at some community medical centers.

A PCO panel, convened by ASCO, examined evidence compiled through a review of the medical research literature - in addition to suggestions by panel members - to develop its recommendation. The PCO will be published online today in the Journal of Clinical Oncology (JCO).

"EGFR testing helps us move toward the goal of tailoring cancer treatments for each patient," said panel co-chair Vicki Keedy, MD, assistant professor of medicine at Vanderbilt-Ingram Cancer Center in Nashville, TN. "We've learned over the years that non-small cell lung cancer is really a collection of genetically distinct diseases. We want to treat patients with drugs that target the molecular drivers of their specific tumors, rather than using a one-size-fits-all approach. But how this approach affects the patients' overall outcome remains uncertain."

Approximately 220,500 new cases of lung cancer occurred in the United States in 2010, with non-small-cell lung cancer making up about 80 percent of cases. Approximately 15 percent of U.S. patients with adenocarcinoma of the lung - a type of non-small-cell lung cancer - carry mutations in the EGFR gene.  EGFR affects cell growth and division, and mutations in the gene can lead to uncontrolled cell division and cancer. Clinical trials have shown that patients with EGFR mutations who are treated with first-line gefitinib and erlotinib benefit from the drugs in terms of tumor response and progression-free survival (PFS), but not overall survival. Neither drug has yet been approved as first-line therapy for lung cancer by the U.S. Food and Drug Administration.

The PCO panel examined the use of EGFR mutation testing in first-line therapy for non-small cell lung cancer in trials comparing an EGFR tyrosine kinase inhibitor to the standard chemotherapy combination of carboplatin and paclitaxel. The major impetus for the PCO was the Iressa Pan-Asian Study (IPASS), a Phase III multicenter trial comparing gefitinib with standard carboplatin and paclitaxel chemotherapy as first-line treatment in patients in East Asia who had advanced non-small cell lung cancer and were either non-smokers or light smokers. ASCO asked the National Cancer Institute's (NCI) Physician Data Query (PDQ) Adult Cancer Editorial Board to assess the trial, and it reported that the study showed that patients given gefitinib as initial therapy had better PFS overall than those receiving chemotherapy.

The IPASS trial found that among patients with negative tests for EGFR mutation, PFS and response rates were greater in patients treated with chemotherapy, while patients with mutated EGFR had better PFS and higher response rates when treated with gefitinib. Although this trial was conducted among Asian patients, outcomes of treatment in patients with mutated EGFR appear to be similar across populations. Four smaller studies examining the use of gefitinib (and in some cases, erlotinib) as first-line treatment reported similar results. None of the studies showed differences in overall survival between those who tested negative for EGFR mutations and those with mutations.

The panel, in its review, acknowledged that erlotinib, which is approved in the United States as second-line therapy, is very similar to gefitinib, which has limited U.S. approval for second-line therapy and is not readily available. For patients with EGFR mutations, drugs such as gefitinib and erlotinib target the mutations that fuel their cancer more specifically than chemotherapy.

"Only a minority of patients with EGFR mutations responds to standard chemotherapy, and while there is some survival benefit, it's not as much as we'd like. We're finding that newer, molecularly targeted drugs like gefitinib and erlotinib are superior options for patients with EGFR mutations," said panel co-chair Giuseppe Giaccone, MD, PhD, chief of the medical oncology branch at the NCI. "On the other hand, for patients who do not have the mutation, giving erlotinib up front is not the right thing to do. It's not as efficacious for those patients, and we may be losing the opportunity to give chemotherapy, which clinical trials have demonstrated to be more effective."

Keedy stressed the importance of designing trials to determine whether first treating a patient who tested negative for an EGFR mutation with a tyrosine kinase inhibitor - which is very likely to be ineffective - delays chemotherapy and affects outcome. Researchers would also like to know if outcome is affected for those patients with an EGFR mutation who are given potentially ineffective chemotherapy, and don't immediately receive treatment with an EGFR tyrosine kinase inhibitor. The PCO pointed to several other research priorities, such as whether there are clinically significant differences between erlotinib and gefitinib among patients with EGFR mutations, since gefitinib is not FDA-approved in the United States.

To view the PCO, click here.

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FDA Aproves New Medical Device for Form of Brain Cancer

April 15 2011

The U.S. Food and Drug Administration recently approved the NovoTTF-100A System, a new device to treat adults with glioblastoma multiforme (GBM) that recurs or progresses after receiving chemotherapy and radiation therapy.

Brain tumors are the growth of abnormal cells in the brain tissue. According to the National Cancer Institute, each year about 19,000 people in the United States are diagnosed with primary brain cancers. In 2010, there were 13,140 deaths from brain and other nervous system cancers in the United States.

GBM is the most common primary brain cancer. The brain tumor is highly resistant to standard treatments such as surgery, radiation and chemotherapy.

When using the NovoTTF-100A System, a health care professional places electrodes on the surface of the patient’s scalp to deliver low-intensity, changing electrical fields called “tumor treatment fields” (TTFs) to the tumor site. The unique shape and electrical characteristics of dividing tumor cells make them susceptible to damage when exposed to TTF, which could stop tumor growth.

The device is portable and can be powered with batteries or plugged into an electrical outlet. Patients can use the device at home, allowing them to continue their normal daily activities.

“Recurrent glioblastoma multiforme is a devastating form of brain cancer that often eludes standard treatments,” said Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health. “The agency’s approval of the NovoTTF-100A System shows FDA’s commitment to innovative new devices that provide patients with other treatment options.”

The FDA based its approval of the NovoTTF-100A System on results from a single international clinical study in 237 patients with recurrent GBM or with GBM that hadn’t responded to traditional therapy. Patients in the study were randomly assigned to receive either the NovoTTF-100A System or chemotherapy treatment.

The study showed comparable overall survival rates between patients treated with the NovoTTF-100A System and those who underwent chemotherapy.

Patients treated with the NovoTTF-100A System experienced a slightly higher incidence of neurological side effects including convulsions and headaches compared to patients receiving chemotherapy. However, they did not experience the significant side effects associated with chemotherapy, including nausea, anemia, fatigue and serious infections.

A survey of patients in the study suggested an improved quality of life in the NovoTTF-100A recurrent GBM patients compared to patients receiving chemotherapy.

Patients should not use the NovoTTF-100A System if they have an implanted medical device or a skull defect, or have a known sensitivity to conductive hydrogels, such as those used with electrocardiograms. The NovoTTF-100A System is not intended to be used in combination with other cancer treatment. The device should only be used after other treatments have failed.

The NovoTTF-100A System is made by Novocure of Portsmouth, NH.

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Breast Cancer Patients' Persistent Fatigue is Real

April 11 2011

COLUMBUS, Ohio – The persistent fatigue that plagues one out of every three breast cancer survivors may be caused by one part of the autonomic nervous system running in overdrive, while the other part fails to slow it down.

That imbalance of a natural system in the body appears linked to the tiredness and exhaustion that can burden cancer patients as much as a decade after their successful treatment.

The effect is so great, researchers say, that it may be a sign of accelerated aging in fatigued patients, causing them to seem as much as 20 years older compared with patients who aren’t fatigued.

Those new research findings, just reported in the journal Psychoneuroendocrinology, are the latest from a three-decade-long study of the impact that stress can have on the human body.

Christopher Fagundes, a postdoctoral fellow at Ohio State University’s Institute of Behavioral Medicine Research (IBMR), and Janice Kiecolt-Glaser, a professor of psychiatry and psychology and a member of the IBMR, drew early data from a larger ongoing study testing whether yoga can combat continuing fatigue in breast cancer patients.

They were looking for a new biomarker, a signal that could point to the initial cause of this fatigue. Their target was the autonomic nervous system, that part of the body that controls unconscious activities like breathing, heartbeat, digestion and such, which earlier research had indicated might play a role.

“When a cancer patient reports persistent fatigue following treatment, it is something that deserves attention. It may be a symptom of other things that matter.”

The autonomic nervous system has two main parts – the sympathetic and the parasympathetic. The former is responsible for what has become known as the fight-or-flight response, a triggering of short-term, energized activity. The latter deals with opposite situations. It is the resting phase, best recognized by the sleepiness that may follow eating a big meal.

While the sympathetic system is an energy hog, the parasympathetic conserves energy, and the two should remain in balance in healthy individuals. The researchers were looking for differences between fatigued and non-fatigued cancer survivors.

“We started looking for biomarkers for cancer-related fatigue,” Fagundes said. “Other research has indicated that a systemic inflammation through the body might be a reliable biomarker for this.

“Sick people with inflammation become tired and lethargic, which makes sense since their bodies are using energy to fight off infections. You can imagine that a long-term, systemic inflammation, year-in and year-out, might produce this fatigue.”

“When a cancer patient reports persistent fatigue following treatment, it is something that deserves attention. It may be a symptom of other things that matter.”

For the study, 109 women participated and were placed in one of two groups – those who reported long-term fatigue and those who didn’t. The women varied from being two months to two years after being treated for their disease.

Fatigue is a normal response to breast cancer treatments like chemotherapy and radiation therapy, but one-third or more of breast cancer survivors report continued debilitating fatigue long after treatment has ended.

After a short relaxation period, each woman had blood drawn to establish a baseline level for norepinephrine, a stress hormone that served as an indicator of activity by the sympathetic nervous system. Each participant had to give a five-minute speech before a two-person panel and then do a series of verbal arithmetic problems aimed at increasing stress levels. Additional blood samples were taken immediately after the stressor and then a half-hour later.

The norepinephrine levels rose as expected from the baseline in both groups after the stressful episode but the researchers were surprised to see something different. Regardless of the stressor, women who had persistent fatigue showed higher levels of norepinephrine than those who weren’t fatigued.

“They had higher sympathetic activity and lower parasympathetic activity,” Fagundes said, an indication that other researchers have suggested is a signal for inflammation.

The researchers also gauged another measure in the study, the natural variability in heart rate which decreases as a person ages. A lessened heart rate variability (HRV) is also an indicator of activity in the parasympathetic, or “resting,” system.

“People who were fatigued had weaker parasympathetic activity than those who weren’t,” he said.

“One of the things we know best is that exercise can enhance a person’s HRV,” Kiecolt-Glaser said. “Exercise is also the best documented treatment for fatigue, so this all begins to make sense.

“Fatigue isn’t a symptom that should be ignored. It’s a marker for other things that might be going on,” she said. Higher norepinephrine levels and lower HRV have been linked to high blood pressure, myocardial infarctions, strokes and diabetes.

“When a cancer patient reports persistent fatigue following treatment, it is something that deserves attention. It may be a symptom of other things that matter.”

Working with Fagundes and Kiecolt-Glaser on the work were William Malarkey, Charles Shapiro, David Murray, Beom Seuk Hwang, Jean Philippe Gouin and Julian Thayer, all from Ohio State; and John Sollers from the University of Auckland.

The work was supported in part by the National Institutes of Health and the American Cancer Society.

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Less Invasive Lymph-node Biopsy Could Prevent Unnecessary Surgery for Patients with Early Stage Endometrial Cancer

April 11 2011

Sentinel-lymph-node (SLN) biopsy can accurately diagnose lymph node status in patients with early stage endometrial cancer and provide vital information on the most effective adjuvant (additional) treatment without the need for complete lymphadenectomy (removal of all the pelvic lymph nodes), thereby reducing the risk of surgical complications. These findings published Online First in The Lancet Oncology, suggest that this minimally invasive procedure is a safe and effective alternative to more extensive lymph node removal.

Accurately determining how far cancer has spread, a process known as staging, is used to plan the most effective treatment for patients. Traditional surgery (lymphadenectomy), involving the removal of all the pelvic lymph nodes, is associated with an increased risk of complications including lymphocysts and lymphoedema (swelling caused by excess fluid build-up), and has shown little benefit in patients with early stage endometrial cancer.

A few small retrospective studies have suggested that doctors could evaluate endometrial cancer using SLN biopsy, a less invasive procedure involving the excision of just a few nodes instead of all regional lymph nodes. During the SLN biopsy, a radioactive colloid and/or blue dye are injected pericervically and follow the path that tumour cells are most likely to take from the tumour to the lymph nodes. The first(s) node(s) to absorb the dye and/or radiocolloid, the sentinel node(s), is removed and biopsied.

The SENTI-ENDO trial was designed to investigate the performance of SLN biopsy at predicting lymph node status in patients with early stage endometrial cancer. Between July, 2007, and August, 2009, 133 patients with early stage endometrial cancer from nine centres across France underwent SLN biopsy followed by complete lymphadenectomy.

SLN was successful in 77% of cases in the right hemipelvis and 76% in the left hemipelvis, with an overall detection rate of 98%.

No false negative cases were recorded in 100% of hemipelvises, so all healthy lymph nodes were correctly identified. Using the patient as the unit of analysis, the less invasive technique produced a negative predictive value (probability that patients who test negative result are correctly diagnosed) of 97% and sensitivity (rate of true positives) of 84%.

No complications were reported during SLN biopsy.

The authors say: “The SLN procedure provides data to tailor adjuvant therapy without increasing the risk of intraoperative and early postoperative complications. Therefore, the SLN procedure alone could be recommended for low-risk and intermediate-risk endometrial cancer.”

They conclude: “Further studies are needed to evaluate the cost-effectiveness of systemic lymphadenectomy compared with lymphoscintigraphy and the SLN procedure, and the effect of the SLN procedure on adjuvant therapies and quality of life.”

In a Comment, Henry Kitchener from The University of Manchester, Manchester, UK suggests that SLN biopsy can now be considered standard care: “The procedure seems feasible (almost 90% of women had detectable SLNs), and it seems reliable in terms of negative predictive value and sensitivity when ultrastaging of SLNs is implemented.”

For full Article and Comment, click here.

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Sleep Issues Contribute to Cognitive Problems in Childhood Cancer Survivors

April 11 2011

A new analysis has found that childhood cancer survivors often suffer from sleep problems and fatigue, which negatively impact their attention and memory. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that addressing sleep hygiene among survivors of childhood cancer may help to improve their cognitive health.

Cognitive problems, such as trouble with attention and memory, often arise in survivors of childhood cancer. These problems, which are either a direct or indirect result of treatment, negatively impact future education, employment, and the ability to live independently.

To assess the effects of fatigue and sleep disruption on cognitive function in long-term survivors of childhood cancer, Kevin Krull, PhD, of St. Jude Children’s Research Hospital in Memphis and his team evaluated a questionnaire filled out by 1,426 individuals from the Childhood Cancer Survivor Study. (The Childhood Cancer Survivor Study was designed to investigate the long-term medical, psychosocial, and functional health of survivors of eight different childhood cancers who were treated between 1970 and 1986.)

Cognitive impairment was identified in over 20 percent of survivors. Study participants’ answers to the questionnaire revealed that long-term survivors of childhood cancer who have problems sleeping or have frequent daytime sleepiness and fatigue are three to four times more likely to have attention and memory problems than survivors who sleep well. “Since survivors are already at increased risk for attention and memory problems, sleep loss and fatigue may make these cognitive problems worse,” said Dr. Krull.

The investigators found that survivors’ cognitive problems that are associated with poor sleep and fatigue are unrelated to the effects of brain radiation, chemotherapy, or the current age of the survivor. Also, cancer survivors who are currently taking antidepressant medications are 50 percent more likely to report attention problems and 70 percent more likely to report memory problems.

“These findings suggest that improved sleep quality and reduced fatigue may help to improve attention and memory functions in survivors,” said Dr. Krull. He added that these results may generalize to survivors of other medical conditions who demonstrate simultaneous sleep and cognitive problems. Krull also cautions that people taking antidepressant medication should not discontinue use without first consulting with a personal physician.

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FDA Approves Orphan Drug Vandetanib

April 07 2011

AstraZeneca today announced that the US Food and Drug Administration (FDA) approved the orphan drug vandetanib for the treatment of medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body.

Vandetanib is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable (non-operable) locally advanced or metastatic disease.The use of vandetanib in patients with indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment-related risks.

“Vandetanib is the only medicine to receive FDA approval specifically for use in patients with advanced medullary thyroid cancer and is the first treatment that AstraZeneca has developed and brought to market under orphan drug designation in the US,” said Howard Hutchinson, Chief Medical Officer, AstraZeneca.

The approval of vandetanib is based on the results of the ZETA study, a Phase III, double-blind trial that randomized 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer to vandetanib 300 mg (n=231) or placebo (n=100). In the study, patients randomized to vandetanib showed a statistically significant improvement in progression-free survival (PFS) when compared to those randomized to placebo (Hazard Ratio [HR]=0.35; 95% Confidence Interval [CI]=0.24-0.53; p<0.0001). This difference reflects a 65% reduction in risk for disease progression. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. At the primary PFS analysis, no significant overall survival difference was noted. QT prolongation, Torsades de pointes, and sudden death are included in the boxed warning for vandetanib. The most common adverse drug reactions (>20%) seen in the ZETA trial with vandetanib were diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain (21%).

A Risk Evaluation and Mitigation Strategy (REMS) is required for vandetanib due to the risks of QT prolongation, Torsades de pointes, and sudden death. Only prescribers and pharmacies who are certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense vandetanib.

Vandetanib received orphan drug designation in medullary thyroid cancer in 2005. Vandetanib is also under regulatory review in the European Union and Canada.

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Just Six Months of Hormone Therapy Doubles Survival Chances When Added to Radiotherapy in Patients with Locally Advanced Prostate Cancer

March 24 2011

Men with locally advanced prostate cancer who are treated with just 6 months of hormone therapy combined with radiotherapy halve their chances of dying from the disease compared with patients who receive radiation alone, according to the long-term (10 year) results of the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial published Online First in The Lancet Oncology. Importantly, these findings also show that 6 months of hormone therapy has few of the adverse side-effects associated with prolonged hormone treatment.

Androgen deprivation therapy (ADT), also known as hormone therapy, is used to treat prostate cancer by lowering the levels of male hormones that can promote the growth of prostate cancer. Supplementary (adjuvant) ADT has been shown to prolong survival in men with locally advanced disease. However, prolonged use of ADT might be associated with significant side-effects which include erectile dysfunction, hot flashes, fatigue, osteoporosis, high cholesterol, anaemia, and cardiac death.

In 2005, initial (5 year) results from the TROG 96.01 trial suggested that short-term neoadjuvant (given before and during radiotherapy) ADT (NADT) significantly improved on the outcome achieved by radiotherapy alone. The trial included 802 men with locally advanced disease who were randomly assigned to prostate external beam radiation alone or with 3 or 6 months of NADT plus radiotherapy.

Five years later, there is still no agreement on the optimum duration of treatment with NADT and clinical practice varies widely.

In this new study, a team from New Zealand and Australia led by Jim Denham from the University of Newcastle, New South Wales, Australia present the long-term outcomes (median follow-up 10.6 years) of the TROG 96.01 trial to establish the size of the benefits from 3 months and 6 months of NADT.

Six months of NADT combined radiotherapy was associated with a significantly lower 10-year prostate-cancer death rate compared with radiation treatment alone (11% vs 22%), and the chances of death due to any cause were reduced by a third (29% vs 43%).

However, 3 months of NADT had no effect on the 10-year rates of distant cancerous spread, prostate-cancer death, or death due to any cause compared with radiation alone.

The authors conclude: “The TROG 96.1 trial…shows that a large proportion of men with locally advanced prostate cancer can be treated successfully, with few late side-effects, with as little as 6 months of NADT (and a relatively low dose of radiation). We believe that 6 months of NADT in combination with contemporary radiation techniques and doses will remain an effective treatment option in the next decade, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.”

In a Comment, Chris Parker from The Royal Marsden Hospital, UK says: “TROG 96.01 is an important trial, and has two clear messages for current clinical practice. First, it confirms that NADT significantly reduces mortality after radiotherapy for high-risk prostate cancer, and is a standard of care. Second, it helps to resolve the uncertainty regarding NADT duration, and strongly suggests that men receiving NADT should have at least 6 months treatment.”

For full article and comment, visit http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70063-8/abstract.

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FDA Approves New Treatment for a Type of Late-stage Skin Cancer

Melanoma patients lived longer with treatment

March 25 2011

The U.S. Food and Drug Administration today approved Yervoy (ipilimumab) to treat patients with late-stage (metastatic) melanoma, the most dangerous type of skin cancer.

Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010 and about 8,700 people died from the disease, according to the National Cancer Institute.

“Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient’s life,” said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. "Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment."

Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously.

Yervoy’s safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed.

The study was designed to measure overall survival, the length of time from when this treatment started until a patient's death. The randomly assigned patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone.

Those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.

Common side effects that can result from autoimmune reactions associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). Severe to fatal autoimmune reactions were seen in 12.9 percent of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.

Due to the unusual and severe side effects associated with Yervoy, the therapy is being approved with a Risk Evaluation and Mitigation Strategy to inform health care professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy's potential side effects.

Yervoy is marketed by New York City-based Bristol-Myers Squibb.

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Penn Researchers Uncover Novel Immune Therapy for Pancreatic Cancer

Drug Stimulates Immune System to Attack “Scaffolding” Around Tumors

March 24 2011

PHILADELPHIA - Researchers at the University of Pennsylvania’s Abramson Cancer Center have discovered a novel way of treating pancreatic cancer by activating the immune system to destroy the cancer’s scaffolding. The strategy was tested in a small cohort of patients with advanced pancreatic cancer, several of whose tumors shrank substantially. The team believes their findings – and the novel way in which they uncovered them -- could lead to quicker, less expensive cancer drug development.

The authors call the results, published in the March 25 issue of Science, a big surprise. “Until this research, we thought the immune system needed to attack the cancer directly in order to be effective,” said senior author Robert H. Vonderheide, MD, DPhil, an associate professor of Medicine in the division of Hematology/Oncology and the Abramson Family Cancer Research Institute. “Now we know that isn’t necessarily so. Attacking the dense tissues surrounding the cancer is another approach, similar to attacking a brick wall by dissolving the mortar in the wall. Ultimately, the immune system was able to eat away at this tissue surrounding the cancer, and the tumors fell apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer.”

The current study is part of a unique research model designed to move back and forth between the bench and the bedside, with the investigative team consisting of researchers based in both the laboratory and in the clinic. In the clinical trial led at Penn by Peter O’Dwyer, MD, professor of Hematology/Oncology, and Gregory L. Beatty, MD, PhD, instructor of Hematology/Oncology, pancreatic cancer patients received standard gemcitabine chemotherapy with an experimental antibody manufactured by Pfizer Corporation. The antibody binds and stimulates a cell surface receptor called CD40, which is a key regulator of T-cell activation. The team initially hypothesized that the CD40 antibodies would turn on the T cells and allow them to attack the tumor.

The treatment appeared to work, with some patients’ tumors shrinking substantially and the vast majority of tumors losing metabolic activity after therapy, although all of the responding patients eventually relapsed. When the researchers looked at post-treatment tumor samples, obtained via biopsy or surgical removal, there were no T cells to be seen. Instead, they saw an abundance of another white blood cell known as macrophages.

To understand what was happening in the tissues of these patients, Vonderheide and Beatty and colleagues turned to a mouse model of pancreatic cancer developed several years ago at Penn. Unlike older mouse models that were simplistic models of human disease, new genetically engineered mice develop spontaneous cancers that are very close reproductions of human tumors. “We can perform preclinical trials in these mice with the same principles we use in our patients,” Vonderheide says, noting that the team even used a randomization protocol to assign individual mice to different arms of the study.

When the investigators treated mice that developed pancreatic cancer with gemcitabine in combination with CD40 antibodies, the results looked like those of the human trial. Some mouse tumors shrank and were found to be loaded with macrophages but contained few or no T cells. Closer inspection showed that the macrophages were attacking what is known as the tumor stroma, the supporting tissue around the tumor. Pancreatic tumors secrete chemical signals that draw macrophages to the tumor site, but if left to their own devices, these macrophages would protect the tumor. However, treating the mice (or patients) with CD40 antibodies seemed to flip that system on its head. “It is something of a Trojan horse approach,” Vonderheide says. “The tumor is still calling in macrophages, but now we’ve used the CD40 receptor to re-educate those macrophages to attack – not promote – the tumor.”

The researchers believe that the CD40 antibodies also activated T cells in the mice, but the T cells couldn’t get into the tumor or its surrounding tissue. “We learned that T cells have a major problem with migration into tumors, and this may be a particular problem for pancreatic cancer,” Vonderheide says. “The area surrounding pancreatic cancers is very dense, fibrotic, and hostile. This is one of the main reasons standard therapies for this disease often work so poorly.”

The researchers are now working on ways to capitalize on their novel information, testing ways to super-charge the macrophage response and to get the T cells into the tumor microenvironment. Vonderheide thinks his team can speed up clinical research by running pilot trials in the mice to test potential therapeutics. Once they understand responses in the mice, then they can use that information to design better human trials.

“Beyond our specific findings, we think these findings point to a new approach for drug development in cancer -- one where we use state-of-the-art mouse models for preclinical trials to guide which trials we should do next in patients,” Vonderheide says. “It should be faster, cheaper and give us a head start in the clinical trials.”