title: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma.
abstract: A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P </= 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.
authors.affiliation: Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany. Westphal@uke.uni-hamburg.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Dana C
authors.initials: DC
authors.lastname: Hilt
authors.forename: Enoch
authors.initials: E
authors.lastname: Bortey
authors.forename: Patrick
authors.initials: P
authors.lastname: Delavault
authors.forename: Robert
authors.initials: R
authors.lastname: Olivares
authors.forename: Peter C
authors.initials: PC
authors.lastname: Warnke
authors.forename: Ian R
authors.initials: IR
authors.lastname: Whittle
authors.forename: Juha
authors.initials: J
authors.lastname: Jääskeläinen
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ram
mesh_terms: D000328:Adult; D000368:Aged; D001672:Biocompatible Materials / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002330:Carmustine / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D004337:Drug Carriers / Q000627:therapeutic use; D004343:Drug Implants; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis; D015996:Survival Rate
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D002330:Carmustine