title: Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Calgary, Calgary, Alberta, Canada; e-mail: jgcairnx@ucalgary.ca
authors.forename: Gregory
authors.initials: G
authors.lastname: Cairncross
authors.forename: Brian
authors.initials: B
authors.lastname: Berkey
authors.forename: Edward
authors.initials: E
authors.lastname: Shaw
authors.forename: Robert
authors.initials: R
authors.lastname: Jenkins
authors.forename: Bernd
authors.initials: B
authors.lastname: Scheithauer
authors.forename: David
authors.initials: D
authors.lastname: Brachman
authors.forename: Jan
authors.initials: J
authors.lastname: Buckner
authors.forename: Karen
authors.initials: K
authors.lastname: Fink
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: Normand
authors.initials: N
authors.lastname: Laperierre
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008130:Lomustine / Q000627:therapeutic use; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D011344:Procarbazine / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011882:Radiotherapy, High-Energy; D016019:Survival Analysis; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine