title: Phase II study of nimustine, carboplatin, vincristine, and interferon-beta with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group.
abstract: OBJECTIVE
  This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFNbeta) chemotherapy.
  
  
  METHODS
  Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNbeta (10 microg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNbeta (10 microg) on Days 8 and 15; and IFNbeta alone (10 microg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNbeta were again administered on the new Day 1 and vincristine and IFNbeta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months).
  
  
  CONCLUSIONS
  The combination of ACNU-carboplatin-vincristine-IFNbeta chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.
authors.affiliation: Department of Neurosurgery, Kitano Hospital Medical Research Institute, Osaka, Japan. tomokazu@kitano-hp.or.jp
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Aoki
authors.forename: Jun A
authors.initials: JA
authors.lastname: Takahashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ueba
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Tsugiya
authors.initials: T
authors.lastname: Fukui
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Masatsune
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016190:Carboplatin / Q000008:administration & dosage; D004361:Drug Tolerance; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D015376:Nimustine; D014750:Vincristine; D016899:Interferon-beta; D016190:Carboplatin