© 2003 by Society
© 2003 by the Society forNeuro-Oncology
A phase 3 trial of local chemotherapy with biodegradable carmustine(BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma
Department of Neurosurgery, University HospitalEppendorf, Hamburg, Germany (M.W.); GuilfordPharmaceuticals, 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 GeneralHospital, Edinburgh, Scotland (I.R.W.); Department ofNeurosurgery, 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 ofNeurosurgery, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg,Germany(Westphal{at}uke.uni-hamburg.de).
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Abstract |
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A previous placebo-controlled trial has shown that biodegradable 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survivalin patients with recurrent glioblastoma multiforme. A previously completedphase 3 trial, also placebo controlled, in 32 patients with newly diagnosedmalignant glioma also demonstrated a survival benefit in those patientstreated with BCNU wafers. Because of the small number of patients in thattrial, a larger phase 3 trial was performed to confirm these results. Twohundred forty patients were randomized to receive either BCNU or placebowafers at the time of primary surgical resection; both groups were treatedwith external beam radiation postoperatively. The two groups were similar forage, sex, Karnofsky performance status (KPS), and tumor histology. Mediansurvival in the intent-to-treat group was 13.9 months for the BCNUwafer-treated group and 11.6 months for the placebo-treated group (log-rankP-value stratified by country = 0.03), with a 29% reduction in therisk of death in the treatment group. When adjusted for factors affectingsurvival, the treatment effect remained positive with a risk reduction of 28%(P = 0.03). Time to decline in KPS and in 10/11 neuroperformancemeasures was statistically significantly prolonged in the BCNU wafer-treatedgroup (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 theplacebo-treated group) and intracranial hypertension (9.1% in the BCNUwafer-treated group vs. 1.7% in the placebo group). This study confirms thatlocal chemotherapy with BCNU wafers is well tolerated and offers a survivalbenefit to patients with newly diagnosed malignant glioma.
Received June 19, 2002; Accepted September 12, 2002
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