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Addition of Chemotherapy to Radiotherapy Continues to Increase Survival in People with Brain Tumors


Giving people with glioblastoma the chemotherapy drug temozolomide in combination with radiotherapy increases their survival compared with those receiving radiotherapy alone, and this improvement persists for up to five years, according to the final results of the EORTC-NCIC trial, published in The Lancet Oncology. For over 30 years, post-operative radiotherapy was the standard treatment for glioblastoma, but it offered only modest survival benefits. The average life-expectancy of people with glioblastoma was 9 to 12 months.

In 2004, after many disappointing attempts with drug therapy, the EORTC-NCIC trial finally showed some promising results, where use of combined treatment with radiotherapy and temozolomide reduced the risk of dying from glioblastoma by 37 percent compared with radiotherapy alone. At two years, 27 percent of people receiving temozolomide in combination with radiotherapy (TMZ/RT) were alive, compared with just 10 percent of those being treated with radiotherapy (RT) alone. However, whether this survival benefit would persist over time was unknown.

In this study, Roger Stupp and colleagues report the five-year outcomes of those involved in the original EORTC-NCIC trial. The authors also examined whether clinical factors and the molecular profile of the tumors would identify people with particularly good survival or response to chemotherapy.

Findings showed that at three years, 16 percent of those receiving TMZ/RT were alive compared with only 4 percent of people having RT alone. At four years, overall survival data after combined treatment were 12.1 percent compared with 3 percent for RT alone, and at five years, 9.8 percent versus 1.9 percent, respectively. Improvement in survival was seen across all clinical prognostic subgroups, even in people considered to have a poor diagnosis.

In exploratory analyses, overall survival data were best in people being treated with TMZ/RT whose tumors carried an inactivated MGMT gene. Almost half of these people were alive after two years, and they also showed a persistent survival advantage at three, four, and five years. The authors suggest that testing tumors for the methylation status of the MGMT gene would allow the selection of those most likely to benefit from this treatment.

The authors caution that upfront combined therapy may be effective in reducing tumor bulk and aggressiveness, but it does not truly modify the natural behavior of the disease, and thus is unlikely to lead to a cure.

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This article was published in Coping® with Cancer magazine, May/June 2009.