Bevacizumab and Irinotecan in the Treatment of Recurrent Malignant Gliomas

Abstract

Rapidly dividing glioma cells maintain adequate oxygen and nutrient delivery through co-opting existing host blood vessels or promoting the formation of new vessels, a process called angiogenesis. Vascular endothelial growth factor is a mediator of hypoxia-induced endothelial cell proliferation and migration and is highly expressed in gliomas, where it acts as a potent regulator of angiogenesis. The use of vascular endothelial growth factor receptor antagonists and vascular endothelial growth factor scavenging antibodies has generated excitement in neuro-oncology because of the rapid but reversible decrease in vascular permeability. This decrease in vascular permeability is marked by a decrease in cerebral edema and a decrease in contrast enhancement visualized on magnetic resonance imaging. These effects on the tumor vasculature are mistakenly referred to as tumor responses because the historical method of measuring tumor response and progression was based on tumor size assessed by contrast permeability through a leaky blood brain barrier. Despite the difficulties in accurately measuring the effect of antivascular endothelial growth factor therapy on tumor viability, several studies confirm that the antivascular endothelial growth factor human monoclonal antibody bevacizumab combined with irinotecan can significantly improve 6-month progression free survival of patients with malignant gliomas compared with historical controls. The impact of cytotoxic chemotherapy on the efficacy of bevacizumab and the effect of this therapy on overall survival are important questions that remain to be answered.