Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial.
OBJECTIVE
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.


CONCLUSIONS
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.
Westphal
M
M
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany. westphal@uke.uni-hamburg.de
Ram
Z
Z
Riddle
V
V
Hilt
D
D
Bortey
E
E
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002330:Carmustine / Q000008:administration & dosage*; D003652:Decanoic Acids / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage*; D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000601:surgery; D005910:Glioma / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000379:methods; D015990:Placebo Effect; D011091:Polyesters / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003652:Decanoic Acids; D004337:Drug Carriers; D011091:Polyesters; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D002330:Carmustine