Radiation therapy chemotherapy combination improves survival in adults with low-grade brain cancer
ROCHESTER, Minn. — Patients with a low-grade type of brain tumor called glioma who received radiation therapy plus a chemotherapy regimen, including procarbazine, lomustine and vincristine (PCV), experienced a longer progression-free survival and overall survival than patients who received radiation therapy alone, according to the results of the clinical trial, Radiation Therapy Oncology Group (RTOG) 9802 published in the April 7 issue of the New England Journal of Medicine.
"This is the first phase III trial to demonstrate conclusively a treatment-related survival benefit for patients with grade 2 glioma," says Jan Buckner, M.D., the study's lead author. Dr. Buckner is an oncologist and chair of the Department of Oncology at the Mayo Clinic Cancer Center in Rochester, Minnesota.
"Our early results, reported at a median patient follow-up of 5.9 years, showed that radiation therapy plus PCV chemotherapy was associated with a statistically significant prolongation of median progression-free survival, but not with overall survival. However, additional follow-up demonstrated an improvement in overall survival as well for these patients," Dr. Buckner says.
Between October 1998 and June 2002, 251 patients with low-grade glioma were enrolled in the RTOG 9802 trial. Patients enrolled were at high risk, compared to other patients with low-grade glioma, because they were 40 or older, or had a less-than-complete surgical removal of their tumor.
Patients were randomized to 1 of 2 trial arms, radiation therapy plus six cycles of PCV chemotherapy or radiation therapy alone. Before treatment, researchers conducted a pathology review on tumor samples and prepared for samples for correlative laboratory studies to assess mutational status and identify prognostic variables.
At a median follow-up time of 11.9 years, 67 percent of enrolled patients were identified as having tumor progression, and 55 percent of patients had died. Patients in the radiation therapy plus PCV chemotherapy arm had longer median survival times, compared with those in the trial arm who received radiation therapy alone (13.3 versus 7.8 years, respectively; p=0.003). Median progression- free survival time for patients receiving radiation therapy plus PCV chemotherapy versus radiation therapy alone was 10.4 years and 4.0 years, respectively. Ten-year, progression-free survival and overall survival rates for patients in the radiation therapy plus PCV chemotherapy arm versus those in the radiation therapy alone arm were 51 percent versus 21 percent and 60 percent versus 40 percent, respectively.
For progression-free survival and overall survival distributions, a difference between treatment arms became apparent only after two to four years following randomization. The favorable prognostic variables researchers identified for progression-free and overall survival included the radiation plus PCV chemotherapy arm and oligodendroglioma histology.
As expected, treatment toxicity was greater in the PCV chemotherapy arm and consistent with patients receiving multiagent chemotherapy regimens. The most common toxicities were fatigue, anorexia, nausea and vomiting, which were mostly grade 1?2 in severity with the exception of grade 3?4 neutropenia.
"Our results indicate that initial radiation therapy followed by PCV is necessary to achieve longer survival in patients with grade 2 glioma and that salvage therapy at relapse after radiation therapy alone is less effective," says Dr. Buckner. "It has also been hypothesized that other genetic alterations may be responsible for a small subset of patients whose glial brain tumors are chemotherapy-resistant. However, radiation therapy plus PCV appears to represent the most effective treatment identified to date for the majority of patients with grade 2 glioma," Dr. Buckner says.
While grade 2 glioma constitute only 5 percent to 10 percent of all brain tumors, they are responsible for progressive neurologic symptoms and premature death in nearly all patients diagnosed with this type of brain tumor.
"RTOG 9802 involves a network of investigators across the U.S. and Canada working through the National Cancer Institute's National Clinical Trials Network," says Dr. Buckner. "This trial could only have been conducted through a publicly funded national clinical trials network."
Funding for the trial was provided by the National Cancer Institute, and the trial was conducted by investigators at institutions participating in the Radiation Therapy Oncology Group, the Alliance for Clinical Trials in Oncology, the Eastern Cooperative Oncology Group and the Southwest Oncology Group.
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