Adding chemotherapy after radiation improves survival for adults with low-grade gliomas

Receiving a chemotherapy regimen following the completion of radiation therapy resulted in longer survival in adults with low-grade gliomas compared with those who received radiation therapy alone. This is the conclusion from long-term follow-up results from a randomized, controlled clinical trial by the Radiation Therapy Oncology Group (RTOG).

Since all three chemotherapy drugs in the regimen are commercially available, the treatment used in the clinical trial is available for use now. However, this form of chemotherapy is associated with toxicities that include reduced white blood cell counts leading to increased infection risk. The trial investigators recommended that it should be used only by physicians experienced in managing the side effects that may occur.

Gliomas are a form of brain tumor. Low-grade gliomas grow more slowly and have a better outcome than the more common type of brain tumor in adults, which is classified as glioblastoma.

The results are being made public now because a long-term follow-up analysis showed significantly longer survival for those people on the trial who received chemotherapy. Full details from this analysis are to be presented at a scientific meeting in 2014 and in a future peer-reviewed publication.

The study, RTOG 9802, enrolled 251 patients with low-grade gliomas between October 1998 and June 2002, to address the role of chemotherapy following radiation treatment. Patients enrolled were at high risk compared with other low-grade glioma patients because they were 40 years or older or had a less than complete surgical removal of their tumor if they were younger than 40 years.

All patients started treatment with surgery followed by radiation therapy. By random assignment, half the patients stopped treatment after radiation therapy and the other half received six cycles of chemotherapy after completing radiation therapy. Patients receiving chemotherapy got three drugs: procarbazine (P); CCNU (C), which generically is known as lomustine; and vincristine (V). This chemotherapy, termed PCV, was given over 21 days and repeated every 8 weeks for a total of six cycles.

A significant improvement in overall survival was noted for study participants who received PCV chemotherapy plus radiation therapy (13. 3 years median survival time) compared with those receiving radiation therapy alone (7.8 years median survival time), which is a difference of 5.5 years. Median follow-up after initial enrollment has been almost 12 years.

Analysis of how patients are doing based on the molecular and genetic characteristics of their tumors is ongoing. These studies will be important because molecular characteristics of related brain tumors have been able to identify patients most likely to benefit from chemotherapy.

“The results of this study are practice-changing,” said colead investigator Jan Buckner, MD, of the Mayo Clinic in Rochester, Minnesota. “Additionally, ongoing analysis of patient tumor samples should allow us to further identify the patients who will, and who will not, benefit from chemotherapy, taking yet another step toward individualized therapy.”

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