Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma

Abstract

Background: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results.

Methods: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy.

Results: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival.

Conclusions: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.).

Figure 1. Randomization, Treatment, and Analysis Populations

PCV denotes procarbazine, lomustine (also called CCNU), and vincristine.

Figure 2. Progression-free Survival, According to Treatment Group

All hazard ratios for the comparison of radiation therapy alone (RT) or radiation therapy plus PCV in the analyses of progression-free survival are for disease progression or death, and all P values are two-sided. Tick marks indicate censored data. There were too few events among patients without the R132H mutation in the isocitrate dehydrogenase 1 gene (IDH1)to assess the association with treatment.

Figure 3. Overall Survival, According to Treatment Group

All hazard ratios in the analyses of overall survival are for death, and all P values are two-sided. Tick marks indicate censored data. There were too few events among patients without the IDH1 R132H mutation to assess the association with treatment.