Gliadel® wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial
M. Westphal1, Z. Ram2, V. Riddle3, D. Hilt4, E. Bortey5 and On behalf of the Executive Committee of the Gliadel® Study Group
||Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany
||Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Turkey
||Pharm Athene, Inc., Maryland, USA
||Ascend Therapeutics, VA, USA
||Athero Genics, Inc., Georgia, USA
Received: 3 December 2004 Accepted: 3 November 2005 Published online: 17 February 2006
Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12–18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel®
wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P
= 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years.
Methods. Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients.
Results. Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group.
Conclusion. Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo.
Keywords: BCNU; brain neoplasms; carmustine; chemotherapy; glioblastoma multiforme; Kaplan-Meier; malignant glioma; neurosurgery; survival analysis