Bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), and irinotecan for treatment of recurrent primary malignant brain tumors in adults

Abstract

12503 Background: The prognosis of recurrent malignant brain tumors is poor, and no efficacious therapy exists in patients previously treated with radiotherapy and standard chemotherapy. Bevacizumab (B) binds to VEGF and inhibits tumor angiogenesis, and treatment with this drug might induce tumor regression and prolongation of life. Irinotecan (I) is a topoisomerase 1 inhibitor with modest effect on recurrent primary brain tumors. The combination of B and I in recurrent malignant gliomas was presented at ASCO 2006 and showed very encouraging responses. Methods: We report confirmatory results of the combination of B and I in a consecutive series of patients with primary malignant brain tumors recurring after standard primary and secondary treatment (surgery, radiotherapy and standard or secondline chemotherapy).With standard inclusion criteria, including PS 0–2, patients received B as 10mg/kg, and I 125 mg/m2 in patients not treated with enzyme inducing antiepileptic drugs (EIAED) or 340 mg/m2 in patients treated with EIAED every other week until progression or non-manageable toxicity. Response evaluation was performed by MacDonald criteria and MRI scans. Results: The results of 31 patients is presented, 15 with grade IV tumors (Glioblastoma multiforme), 7 with grade III anaplastic astrocytomas, 5 with anaplastic oligodendrogliomas, 1 with anaplastic ependymoma, 1 with hemangiopericytoma, 1 with prolactinoma, and 1 with medulloblastoma. Four patients had complete response, 3 grade IV tumors and 1 anaplastic oligodendroglioma. One patient had partial response (> 50% tumor reduction), 12 had stable disease (3 had tumor reduction between 31 - 45 %). 14 progressed. No grade 4 toxicity was observed and most patients experienced grade 1–2 toxicity. Two tromboembolic events and 1 intestinal perforation were observed. Conclusion: The combination of B and I is safe, induces tumor regression in a substantial number of patients, and can be used as treatment to patients recurring after standard treatment. No significant financial relationships to disclose.