Bevacizumab: A treatment option for recurrent glioblastoma multiforme

OBJECTIVE: To review the available literature evaluating the effect of bevacizumab on progression-free survival when used in combination with irinotecan for recurrent glioblastoma multiforme (GBM). DATA SOURCES: Searches of MEDLINE (1966-June 2008), the Cochrane Library, and International Pharmaceutical Abstracts (1970-June 2008) were conducted using the terms bevacizumab, irinotecan, and glioblastoma multiforme. STUDY SELECTION AND DATA EXTRACTION: The search was limited to studies conducted in humans. All articles identified from the data sources were evaluated. All clinical trials evaluating the efficacy and safety of bevacizumab in the treatment of recurrent GBM were included in the review. DATA SYNTHESIS: Hypoxia, mutagenesis, and the secretion of various growth factors can all lead to production of vascular endothelial growth factor (VEGF), a proangiogenic growth factor, and angiogenesis in GBM. Neoplastic progression is dependent on angiogenesis, and anti-VEGF therapy has been successful in multiple disease states. However, there are currently no available anti-VEGF therapies approved for treatment of GBM. Bevacizumab is a humanized monoclonal antibody that binds to and inhibits the activity of VEGF When compared with data from clinical trials that use single chemotherapeutic agents in recurrent GBM, the addition of bevacizumab to cytotoxic chemotherapy, such as irinotecan, appears to improve progression-free survival in patents progressing on the standard of care, with a 6-month progression-free survival rate of 46%. Bevacizumab is well tolerated by most patients, with modest risk (11% in Phase 2 trials) of venous thromboembolism. CONCLUSIONS: Although the combination of bevacizumab and irinotecan is producing positive results in patients with recurrent GBM, larger, randomized clinical trials need to be performed to determine the magnitude of the benefit from bevacizumab. Bevacizumab administered biweekly at a dose of 10 mg/kg in combination with irinotecan may improve progression-free survival.