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. 2012 Sep 1;30(25):3065-70. doi: 10.1200/JCO.2011.35.8598. Epub 2012 Jul 30.

Abstract

Purpose: A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).

Patients and methods: Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests.

Results: In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02).

Conclusion: PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chi-Square Distribution
  • Disease-Free Survival
  • Glioma / mortality
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Lomustine / administration & dosage
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Procarbazine / administration & dosage
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Supratentorial Neoplasms / mortality
  • Supratentorial Neoplasms / pathology
  • Supratentorial Neoplasms / therapy*
  • Time Factors
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Procarbazine
  • Vincristine
  • Lomustine