Treatment > Carmustine

Abstract

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Manfred Westphal, Dana C. Hilt, Enoch Bortey, Patrick Delavault, Robert Olivares, Peter C. Warnke, Ian R. Whittle, Juha Jääskeläinen, Zvi Ram

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.

© 2003 Duke University Press