Combination Therapy Improves Survival in Brain Cancer

Radiation therapy plus chemotherapy extends overall survival in patients with grade 2 glioma.

A clinical trial published in the New England Journal of Medicine found that patients with glioma who had received both radiation therapy and chemotherapy, including procarbazine, lomustine, and vincristine (PCV), experienced improved overall survival (OS).

Grade 2 glioma is a low-grade type of brain tumor that accounts for just 5% to 10% of all tumors. However, these tumors are responsible for progressive neurologic symptoms and premature death in majority of patients who are diagnosed.

“This is the first phase 3 trial to demonstrate conclusively a treatment-related survival benefit for patients with grade 2 glioma,” said lead study author Jan Buckner, MD.

In the study, researchers enrolled 251 low-grade glioma patients between October 1998 and June 2002 into the RTOG 9802 trial. Those enrolled were high risk compared with other patients with glioma, because of their age (40 years or older) or they had a incomplete surgical removal of their tumor.

Patients were randomized to receive either radiation therapy plus 6 cycles of PCV chemotherapy or radiation alone. Prior to the start of treatment, researchers conducted a pathology review on tumor samples and prepared samples for correlative laboratory studies to determine mutational status and identify prognostic variables.

The results of the study showed that during the median follow up of 11.9 years, 67% of patients had tumor progression, while 55% died.

Patients in the radiation and chemotherapy combination group had longer median survival rates compared with those who received radiation alone (13.3 versus 7.8 years, respectively; p=0.003).

Patients administered radiation therapy plus PCV chemotherapy compared with radiation therapy alone had a median progression-free survival (PFS) time of 10.4 years and 4 years, respectively. The 10-year PFS and OS rates were 51% versus 21%, respectively, and 60% versus 40%, respectively.

“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,” Buckner said. “However, additional follow-up demonstrated an improvement in overall survival as well for these patients.”

When it came to PFS and OS distributions, there was a difference in treatment that became apparent after 2 to 4 years following randomization. Favorable prognostic variables identified included radiation plus chemotherapy and oligodendroglioma histology.

The most common toxicities included: anorexia, fatigue, nausea, and vomiting, which were mostly grade 1/2 in severity, with the exception of grade 3/4 neutropenia. Treatment toxicity was found to be greater in the PCV chemotherapy group, with patients receiving multi-agent chemotherapy treatments.

“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,” Buckner said. “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.”