title: Phase III study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Cooperative Oncology Group Trial 2394.
abstract: OBJECTIVE
  This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU.
  
  
  METHODS
  A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection.
  
  
  RESULTS
  The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P =.33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P <.01).
  
  
  CONCLUSIONS
  This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy.
authors.affiliation: 1650 Orleans St, Room G93, The Sydney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. grossman@jhmi.edu
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
authors.forename: Anne
authors.initials: A
authors.lastname: O'Neill
authors.forename: Margaret
authors.initials: M
authors.lastname: Grunnet
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.forename: James L
authors.initials: JL
authors.lastname: Pearlman
authors.forename: Henry
authors.initials: H
authors.lastname: Wagner
authors.forename: Mark
authors.initials: M
authors.lastname: Gilbert
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Newton
authors.forename: Richard
authors.initials: R
authors.lastname: Hellman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D002330:Carmustine