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 intentto-treat group was 13.9 months for the BCNU wafertreated 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. Neuro-Oncology 5, 79-88, 2003 (Posted to Neuro-Oncology [serial online], Doc. 02-023, February 10, 2003 P resently, malignant gliomas are treated by resection, external beam radiation, and, in some cases, systemic chemotherapy (Cairncross et al

Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors

“…Most patients receive standard treatment of radiation with concurrent chemotherapy of temozolomide, followed by adjuvant temozolomide. Approved second-line therapies for G B include intravenous bevacizumab [2] and carmustine wafers [3] (the latter, if surgical gross total resection of the recurrence is feasible). Re-irradiation may add benefit to selected cases [4,5] and ongoing studies (RTOG 1205) continue to evaluate the benefit of this approach.…”

Clinical trials in neurosurgical oncology

“…Randomized controlled trials comparing post-resection implantation of carmustine (BCNU) impregnated polymer wafers (Gliadel wafers) with resection alone for recurrent malignant glioma revealed a modest increase in survival in the absence of temozolomide. Median survival was prolonged by 8 weeks (31 weeks in patients receiving the chemo wafer therapy compared to 23 weeks in patients undergoing resection alone) [61,62]. Recently, a single institution review of over 1,000 patients with malignant astrocytoma of whom 28 % who received Gliadel wafers was performed [63].…”

Glioblastomas: molecular aspects and current management

“…Une é tude de phase III contre placebo à la ré cidive a montré que cette straté gie permettait un allongement de la survie de deux mois [7]. Suite à une autre é tude de phase III contre placebo, le Gliadel ® a é galement obtenu l'AMM pour le traitement de premiè re ligne des GB en complé ment d'une radiothé rapie standard [35]. Bien qu'il n'existe pas d'é tude comparative, l'opinion de nombreux neuro-oncologues est que l'efficacité de cette straté gie semble moins importante que celle de la RTCT selon le protocole de Stupp [11].…”