title: A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.
abstract: OBJECTIVE
  This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%.
  
  
  METHODS
  In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001).
  
  
  CONCLUSIONS
  (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Halperin
authors.forename: J
authors.initials: J
authors.lastname: Herndon
authors.forename: S C
authors.initials: SC
authors.lastname: Schold
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: N
authors.initials: N
authors.lastname: Vick
authors.forename: J G
authors.initials: JG
authors.lastname: Cairncross
authors.forename: D R
authors.initials: DR
authors.lastname: Macdonald
authors.forename: L
authors.initials: L
authors.lastname: Gaspar
authors.forename: B
authors.initials: B
authors.lastname: Fischer
authors.forename: E
authors.initials: E
authors.lastname: Dropcho
authors.forename: S
authors.initials: S
authors.lastname: Rosenfeld
authors.forename: R
authors.initials: R
authors.lastname: Morowitz
authors.forename: J
authors.initials: J
authors.lastname: Piepmeier
authors.forename: W
authors.initials: W
authors.lastname: Hait
authors.forename: T
authors.initials: T
authors.lastname: Byrne
authors.forename: M
authors.initials: M
authors.lastname: Salter
authors.forename: J
authors.initials: J
authors.lastname: Imperato
authors.forename: J
authors.initials: J
authors.lastname: Khandekar
authors.forename: N
authors.initials: N
authors.lastname: Paleologos
authors.forename: P
authors.initials: P
authors.lastname: Burger
authors.forename: G C
authors.initials: GC
authors.lastname: Bentel
authors.forename: A
authors.initials: A
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011446:Prospective Studies; D011785:Quality Assurance, Health Care; D015996:Survival Rate
chemical_list: D016685:Mitomycin; D015122:Mercaptopurine; D002330:Carmustine