title: Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study.
abstract: The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94143, USA. pradosm@neurosurg.ucsf.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
authors.forename: Harry S
authors.initials: HS
authors.lastname: Greenberg
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Nicholas
authors.forename: H Ian
authors.initials: HI
authors.lastname: Robins
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: Karen L
authors.initials: KL
authors.lastname: Fink
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jaeckle
authors.forename: John
authors.initials: J
authors.lastname: Kuhn
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: S Clifford
authors.initials: SC
authors.lastname: Schold
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D016001:Confidence Intervals; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009656:North America; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide