Safety of bevacizumab in advanced ovarian and müllerian cancers: A review

Despite the armamentarium of cytotoxic agents available in the treatment of patients with advanced recurrent ovarian, fallopian, and peritoneal disease, enthusiasm for these agents has been tempered by their toxicity profile, poor response rate, and eventually, the emergence of resistance. In recent years, focus has shifted to an understanding of signaling pathways that promote angiogenesis. Tumor angiogenesis is well established as essential for the growth and metastasis of solid tumors. This process involves the recruitment of mature vasculature and circulating endothelial cells and proangiogenic soluble mediators, one of which includes the vascular endothelial growth factor (VEGF). This factor has several known activities, such as mitogenesis, angiogenesis, endothelial survival, enhancement of vascular permeability, and effects on hemodynamic status. Vascular endothelial growth factor is a 45-kDA glycoprotein that is regulated by oxygen tension and also by various growth factors, hormones, and oncogenes. Inhibiting VEGF and its action has been the focus of intense research in several disciplines and has emerged as an attractive focus for the design of targeted therapeutics in the field of ovarian cancer. Numerous agents targeting angiogenesis are currently being explored. These include monoclonal antibodies to the VEGF ligand, small tyrosine kinase inhibitors that target the vascular endothelial receptor, and soluble decoy VEGF receptors. The most studied agent to date has been bevacizumab, a recombinant humanized monoclonal antibody to the VEGF ligand. Although the efficacy of this agent has been well established in multiple disciplines, several concerns have been raised as to the unique adverse effects of this agent.