Chemotherapy plus Radiation Improved Progression-free Survival in Adults with Low-grade Glioma

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Adult patients with supratentorial low-grade glioma who received chemotherapy with PCV (procarbazine [Matulane], lomustine [CeeNu], and vincristine) in addition to radiation therapy had improved progression-free survival but not overall survival compared to patients receiving radiotherapy alone, according to initial results of the Radiation Therapy Oncology Group (RTOG) 9802 trial. “On post hoc analysis, for 2-year survivors, the addition of PCV to [radiotherapy] conferred a survival advantage, suggesting a delayed benefit for chemotherapy,” the researchers reported in the Journal of Clinical Oncology.1

All patients received the same radiotherapy: 54 Gy given over 6 weeks in 30 fractions of 1.8 Gy. Patients randomly assigned to chemotherapy received six cycles of postradiation procarbazine (60 mg/m2 orally per day on days 8 through 21 of each cycle), lomustine (110 mg/m2 orally on day 1 of each cycle), and vincristine (1.4 mg/m2 [maximum, 2 mg]) intravenously on days 8 and 29 of each cycle. Each cycle was 8 weeks.

Key Findings

The median overall survival time was 7.5 years for the 126 patients allocated to the radiotherapy-only arm and more than 8.5 years but not yet reached for the radiotherapy-plus-PCV arm. The 2-year and 5-year overall survival rates were 85% and 72% for patients who received radiotherapy plus PCV vs 87% and 63% for those who received radiotherapy alone. Radiotherapy plus PCV did not improve overall survival (the primary endpoint) vs radiotherapy alone. “Therefore, the trial is negative,” the investigators concluded. “A positive trial would have required a shift in 5-year survival from 70% to 85% (a relative increase of 21%); in reality, the 5-year survival values were 63% vs 72%, a relative increase of 14%.”

The median progression-free survival time was more than 6.1 years, but not yet reached for the radiotherapy-plus-PCV arm vs 4.4 years for radiotherapy alone. The 2-year and 5-year progression-free survival rates were 74% and 63% for patients who received radiotherapy plus PCV vs 75% and 46% for those who received radiotherapy alone. “In the initial 2-year follow-up phase, the [overall survival] curves for the two regimens actually cross,” the researchers reported, and “a similar trend is observed for [progression-free survival].”

Among the 211 patients who survived 2 years, overall and progression-free survival rates were similar for patients in both study arms for the first 2 years, “although crossing of the curves did occur,” the authors noted. “However, beyond 2 years, the survival curves separated significantly, with both [overall and progression-free survival] favoring patients treated with PCV [plus radiotherapy],” the authors stated. In a post hoc analysis of a subset, the addition of PCV to radiation “reduced the risk of death by 48% and progression by 56%, suggesting possible delayed benefits for chemotherapy.” ■


1. Shaw EG, Wang M, Coons SW, et al: Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: Initial results of RTOG 9802. J Clin Oncol. July 30, 2012 (early release online).




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