Bevacizumab: A Controversial Agent Against High-Grade Gliomas

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Despite the current regimen of surgical resection with subsequent external beam radiotherapy and temozolomide, mean survival is 14.6 months and 2-year survival is 26%. GBM is a highly vascular tumor, a result of its increased expression of vascular endothelial growth factor (VEGF) compared to other brain tumors. VEGF promotes endothelial cell proliferation, and is thought to have a pivotal role during tumor progression. Multiple treatment modalities have targeted VEGF and VEGF receptors (VEGFTs) due to their essential roles in the regulation of angiogenic processes. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF. Positive results from Phase II clinical trials with bevacizumab for recurrent GBM led to its U.S. Food and Drug Administration approval. Bevacizumab can produce significant decrease in contrast enhancement as early as 1 to 2 days after the beginning of treatment, and often results in radiologic response rates of 25% to 60%. However, it has been noted that rapid improvement in radiographic response is not directly correlated to decreased tumor burden or improved survival. Furthermore, there are significant adverse effects associated with this agent that must be considered when tailoring therapy. These topics and current studies evaluating the use of bevacizumab for high-grade gliomas are discussed