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.