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Clinical Therapy Trials—Drugs |
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany (M.W.); Guilford Pharmaceuticals, Baltimore, MD 21224, USA (D.C.H., E.B.); Aventis Pharma France, Paris, France (P.D., R.O.); Walton Centre for Neurology and Neurosurgery, Liverpool, UK (P.C.W.); Department of Neurosurgery, Western General Hospital, Edinburgh, Scotland (I.R.W.); Department of Neurosurgery, Topeliuksenkatu 5, Helsinki, Finland (J.J.); Department of Neurosurgery, Chaim Sheba Medical Center, Tel-Aviv, Israel (Z.R.)
3 Address correspondence and reprint requests to Manfred Westphal, Department of Neurosurgery, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (Westphal{at}uke.uni-hamburg.de).
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.
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