title: Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme.
abstract: OBJECTIVE
  To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors.
  
  
  METHODS
  Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m2 carboplatin for two 5-day cycles separated by 2 weeks; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed.
  
  
  RESULTS
  Eighty-three patients were evaluable for analysis. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 of 74), and biopsy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those > or = 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariates individually predictive of improved survival were younger age (p < 0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ("radiation necrosis").
  
  
  CONCLUSIONS
  When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients.
authors.affiliation: Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Levin
authors.forename: M H
authors.initials: MH
authors.lastname: Maor
authors.forename: P F
authors.initials: PF
authors.lastname: Thall
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: J
authors.initials: J
authors.lastname: Bruner
authors.forename: R
authors.initials: R
authors.lastname: Sawaya
authors.forename: A P
authors.initials: AP
authors.lastname: Kyritsis
authors.forename: N
authors.initials: N
authors.lastname: Leeds
authors.forename: S
authors.initials: S
authors.lastname: Woo
authors.forename: L
authors.initials: L
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016190:Carboplatin / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D016190:Carboplatin