Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402

J Clin Oncol. 2006 Jun 20;24(18):2707-14. doi: 10.1200/JCO.2005.04.3414.


Purpose: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are treated with surgery and radiotherapy (RT) at diagnosis, but they also respond to procarbazine, lomustine, and vincristine (PCV), raising the possibility that early chemotherapy will improve survival. Furthermore, better outcomes in AO have been associated with 1p and 19q allelic loss.

Patients and methods: Patients with AO and AOA were randomly assigned to PCV chemotherapy followed by RT versus postoperative RT alone. The primary end point was overall survival. The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization.

Results: Two hundred eighty-nine eligible patients were randomly assigned to either PCV plus RT (n = 147) or RT alone (n = 142). At progression, 80% of patients randomly assigned to RT had chemotherapy. With 3-year follow-up on most patients, the median survival times were similar (4.9 years after PCV plus RT v 4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI, 0.66 to 1.24; P = .26). Progression-free survival time favored PCV plus RT (2.6 years v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91; P = .004), but 65% of patients experienced grade 3 or 4 toxicity, and one patient died. Patients with tumors lacking 1p and 19q (46%) compared with tumors not lacking 1p and 19q had longer median survival times (> 7 v 2.8 years, respectively; P < or = .001); longer progression-free survival was most apparent in this subset.

Conclusion: For patients with AO and AOA, PCV plus RT does not prolong survival. Longer progression-free survival after PCV plus RT is associated with significant toxicity. Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 19
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Lomustine / therapeutic use
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Oligodendroglioma / drug therapy*
  • Oligodendroglioma / genetics
  • Oligodendroglioma / radiotherapy*
  • Oligodendroglioma / surgery
  • Procarbazine / therapeutic use
  • Proportional Hazards Models
  • Radiotherapy, High-Energy
  • Survival Analysis
  • Vincristine / therapeutic use


  • Procarbazine
  • Vincristine
  • Lomustine

Supplementary concepts

  • PCV protocol