A phase I trial of surgery, Gliadel wafer implantation, and immediate postoperative carboplatin in combination with radiation therapy for primary anaplastic astrocytoma or glioblastoma multiforme.

Two types of chemotherapy used in the treatment of patients with malignant glioma are carboplatin and Gliadel wafer [(3.85% 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU)]. To date there have been no published data examining their concurrent use in this disease. The purpose of this study was to evaluate combination chemotherapy with Gliadel wafer and carboplatin in patients with high-grade, malignant glioma. In this prospective phase I study, 16 patients underwent surgery, Gliadel wafer implantation (up to 8 wafers), intravenous carboplatin given postoperatively (day 3 or 4) at a dose escalation range of area under the curve (AUC)=2-6, and external beam radiation. Median age was 55 years (range 27-66 years). Fourteen (88%) patients had glioblastoma multiforme and 2 (12%) had anaplastic astrocytoma. Performance status was as follows: Eastern Cooperative Oncology Group (ECOG)=0 (2 patients), ECOG=1 (13 patients), and ECOG=2 (2 patients). Three patients were treated at each dosing level (AUC=2-6), and 4 patients were treated at an AUC=5. Carboplatin was administered to all patients by postoperative day 4. Radiation was begun on day 14-36. No grade 3 or 4 toxicities were noted in this study. Median progression-free and overall survival was 266 and 679 days, respectively. We conclude that administering systemic carboplatin is safe and well tolerated in the postoperative period immediately following resection and implantation of Gliadel wafer for the treatment of malignant glioma. Further evaluation in a phase II setting, at maximal carboplatin dose to establish potential efficacy, with this combination is warranted.