Adding chemotherapy to radiation doubles survival time for some brain tumor patients
The addition of chemotherapy to radiation therapy nearly doubled median survival time for patients with anaplastic oligodendroglioma, a rare type of brain tumor, containing a genetic abnormality known as the 1p19q co-deletion. The finding, from a phase III trial in which patients were followed for a median of 11 years, may result in changes to at least one ongoing National Cancer Institute-sponsored clinical trial. NCI and the Radiation Therapy Oncology Group (RTOG) announced the finding Jan. 19.
Dr. Walter J. Curran, Jr., executive director of Winship Cancer Institute of Emory University, was a senior author of the study. Curran is also group chairman of RTOG.
Among patients whose tumors carried the abnormality, those treated with chemotherapy and radiation survived for a median of 14.7 years, compared with 7.3 years for those who received radiation alone.
Investigators took the unusual step of announcing the findings publicly before presenting them at a scientific meeting because of their significance for the treatment of other patients with brain tumors, including patients enrolled in an ongoing phase III clinical trial.
“We wanted to share this information to ensure that patients have access to the most effective therapy,” said Dr. Curran. RTOG conducted the trial, known as RTOG 9402, in collaboration with four other NCI-sponsored cooperative groups.
The new findings mean that “initial management with radiation and chemotherapy should be considered the standard of care [for patients with the co-deletion] because of the survival benefit,” said Dr. Curran.
In the trial, which began in 1994, 286 patients with anaplastic oligodendrogliomas, tumors that form in the brain’s nerve tissue, were randomly assigned to receive either standard therapy with radiation alone or radiation plus a multidrug chemotherapy regimen consisting of the drugs procarbazine, lomustine, and vincristine (PCV).
Results with a minimum follow-up time of 3 years, published in 2006, showed no overall survival benefit for patients who received chemotherapy. Regardless of treatment assignment, however, patients whose tumors carried the 1p19q co-deletion survived significantly longer than patients whose tumors did not have the co-deletion (more than 7 years versus 2.8 years).
The new analysis, based on longer follow-up, provides “unequivocal evidence that the chromosomal structure of 1p and 19q co-deletion can be used as a marker to determine which patients will benefit from combined chemotherapy and radiation therapy,” said principal investigator Dr. Gregory Cairncross of the University of Calgary in Canada.
Oligodendrogliomas make up about 9 percent of all primary tumors of the brain and central nervous system. They occur primarily in adults; the average age at diagnosis is 35. Roughly half of patients have tumors that contain the 1p19q co-deletion, in which parts of chromosomes 1 and 19 are simultaneously deleted.
For patients whose tumors contained only one chromosomal deletion (either 1p or 19q) or no deletion, survival was similar whether they received radiation alone or radiation plus chemotherapy (2.6 years versus 2.7 years).
Announcement of the findings resulted in an immediate suspension of enrollment into an ongoing NCI-sponsored clinical trial in which patients with anaplastic gliomas are being randomly assigned to treatment with radiation alone or radiation plus chemotherapy with the drug temozolomide. This trial, dubbed CODEL, is enrolling only patients whose tumors carry the 1p19q co-deletion.
“We cannot in good faith continue randomly assigning patients to the radiation-only treatment arm now that we know chemotherapy plus radiation is superior,” said Dr. Malcolm Smith of NCI’s Cancer Therapy Evaluation Program, which oversees trials conducted by NCI-supported cooperative groups. “Patients not enrolled in clinical trials should also benefit from this new information.”
Dr. Cairncross and his co-authors have submitted an abstract of the trial results for presentation at the American Society of Clinical Oncology annual scientific meeting in Chicago in June.