Abstract

Glioblastoma multiforme (GBM) is the most aggressive cancer and has the worst prognosis of all malignant gliomas at diagnosis. At the time of disease recurrence/progression, GBM has an even worse prognosis. Vascular proliferation is an important marker in the histological grading of gliomas. Malignant gliomas overexpress VEGF, the principal mediator of tumor angiogenesis, the levels of which correlate directly with tumor vascularity and grade, and inversely with prognosis. Bevacizumab is a humanized monoclonal antibody against VEGF. Bevacizumab with irinotecan has been approved by the US Food and Drug Administration (FDA) for colorectal cancer. Bevacizumab is also FDA approved as a first line treatment for nonsmall cell lung cancer in combination with carboplatin and paclitaxel, has obtained accelerated approval for metastatic HER2-negative breast cancer patients in combination with paclitaxel, and most recently, accelerated approval for recurrent glioblastoma multiforme as single agent. In the first FDA approved phase II trial for recurrent malignant glioma patients published patients received irinotecan [125 mg/m2 for patients on non enzyme inducing antiepileptic drug (EIAED) or not on an antiepileptic drug, and 340 mg/m2 for patients on EIAED] intravenously (IV) every two weeks in combination with bevacizumab 10 mg/kg IV every two weeks. Thirty-two patients were enrolled and a radiographic response rate of 63% was observed [1 complete response (CR) and 19 partial responses (PRs)]. A 6-month PFS of 38% for all patients and a 6-month overall survival of 72% were observed. Following these findings, multiple studies with irinotecan and other agents more commonly used in malignant gliomas were initiated to evaluate alternative bevacizumab-based regimens for recurrent malignant glioma patients. In the vast majority, all those studies showed an unprecedented increase in PFS and response rate in malignant glioma patients treated with bevacizumab as a single agent or in combination, as well a significant improvement in the quality of life of the patients exposed to bevacizumab. However, the utilization of a bevacizumab based regimen for recurrent malignant gliomas has opened a brand new field in neuro-oncology. Further study is needed to determine optimal managements and enhance the quality of life for these patients.