Phase II study of bevacizumab plus irinotecan and carboplatin for recurrent WHO grade 3 malignant gliomas with no prior bevacizumab failure.

Abstract

2095^ Background: No standard treatment exists for recurrent WHO grade 3 malignant glioma patients. Bevacizumab (BV) with irinotecan has significant anti-tumor activity for recurrent glioblastoma. Carboplatin has anti-glioma activity and can potentiate the cytotoxicity of irinotecan. We evaluated the progression-free survival (PFS) of BV in combination to irinotecan and carboplatin in recurrent WHO grade 3 malignant gliomas, as well as its safety. Methods: Adult patients with measurable recurrent WHO grade 3 malignant glioma, ≥12 weeks after radiation therapy, ≥4 weeks after chemotherapy, with adequate organ function, KPS ≥70%, no prior failure or grade ≥3 toxicity to the agents, and no contraindications to BV were eligible for study. Patients received BV at 10 mg/kg with irinotecan on days 1 and 15 of a 28-day cycle. The dose of irinotecan was 125 mg/m2 for patients not on enzyme inducing anti-epileptics (EIAEDs) and 340 mg/m2 for patients on EIAEDs. All patients received carboplatin at an AUC of 4 on day 1 of each cycle. MRIs were obtained every 8 weeks. Results: As planned, 39 WHO grade III malignant glioma patients were enrolled on study. Median age was 47 (range, 26-71). At a median follow up of 14 months, the 6-month PFS is 69% and the median PFS is 11 months. A median of 8 cycles were given. Seven patients completed the planned course of treatment (12 cycles) with hypometabolic PET scan and nine patients remain on study. Fifteen patients came off study due to disease progression and eight due to toxicity. As of 1/25/2012, 22 patients are still alive and 17 have died. Grade 3-4 toxicities included: neutropenia (grade 3, n=12; grade 4, n= 1), thrombocytopenia (grade 3, n=6; grade 4, n=4), nausea (grade 3, n=7), diarrhea (grade 3, n=2), deep venous thrombosis (grade 3, n=2), febrile neutropenia (grade 3, n=1; grade 4, n=1), fatigue (grade 3, n=8; grade 4, n=1), cerebral infarction (grade 4, n=3), intracranial hemorrhage (grade 4, n=1), posterior reversible encephalopathy syndrome (grade 3, n=1). Conclusions: The combination of bevacizumab, irinotecan and carboplatin for WHO grade 3 malignant glioma patients is effective and with no more than expected toxicity.