title: Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme.
abstract: BACKGROUND
  The aim of this study was to evaluate the efficacy and safety of carmustine (BCNU) in combination with temozolomide as first-line chemotherapy before and after radiotherapy (RT) in patients with inoperable, newly diagnosed glioblastoma multiforme (GBM).
  
  
  METHODS
  Forty patients were treated with BCNU (150 mg/m2) on day 1 and temozolomide (110 mg/m2/day) on days 1 through 5 of each 42-day cycle for up to four cycles prior to conventional RT (2 Gy fractions to a total of 60 Gy). After RT, BCNU + temozolomide was administered for four additional cycles or until progression. The primary end point was response rate; secondary end points included progression-free survival (PFS); overall survival (OS) and safety.
  
  
  RESULTS
  Sixty per cent of patients completed four cycles of neo-adjuvant BCNU + temozolomide. Objective response rate (intention-to-treat) was 42.5% (95% confidence interval 27% to 58%), including two (5%) complete and 15 (37.5%) partial responses. In the eligible population (n=37) the objective response rate was 46%. Nine (24%) patients had stable disease and 14 (35%) had progressive disease. Median PFS and OS were 7.4 and 12.7 months, respectively. Age was the only significant prognostic factor and tumor location (lobar versus multifocal versus corpus callosum) showed a trend. Grade 3-4 toxicities included thrombocytopenia (n=11) and neutropenia (n=7) for both pre- and post-RT chemotherapy. Four patients required platelet transfusions. No patient discontinued treatment because of toxicity.
  
  
  CONCLUSIONS
  The combination of BCNU plus temozolomide as neo-adjuvant therapy in inoperable GBM exhibited promising activity with a good safety profile and warrants further evaluation.
authors.affiliation: Unité de Neuro-Oncologie, Service de Neurochirurgie, CHU Timone, Assistance Publique-Hôpitaux de Marseille, Service de Pharmacie, CHU Timone, cedex France.
authors.forename: M
authors.initials: M
authors.lastname: Barrié
authors.forename: C
authors.initials: C
authors.lastname: Couprie
authors.forename: H
authors.initials: H
authors.lastname: Dufour
authors.forename: D
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: X
authors.initials: X
authors.lastname: Muracciole
authors.forename: K
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: D
authors.initials: D
authors.lastname: Braguer
authors.forename: P M
authors.initials: PM
authors.lastname: Martin
authors.forename: J C
authors.initials: JC
authors.lastname: Peragut
authors.forename: F
authors.initials: F
authors.lastname: Grisoli
authors.forename: O
authors.initials: O
authors.lastname: Chinot
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide