Intricacies of Bevacizumab-induced Toxicities and Their Management

OBJECTIVE: To review the serious and common toxicities of bevacizumab and describe their incidence, risk factors, presentation, pathophysiology, and management. DATA SOURCES: Literature for this review article was collected from PubMed, MEDLINE, and the proceedings of the American Society of Clinical Oncology (2000-November 2008). The key terms used in the search were: bevacizumab, vascular endothelial growth factor, angiogenesis inhibitors, toxicity, toxicity management, and adverse event. STUDY SELECTION AND DATA EXTRACTION: Review articles, preclinical studies, and all published Phase 1-3 clinical trials were reviewed. The references listed in identified articles were examined for additional publications. DATA SYNTHESIS: The biomedical literature from 2000 to 2008 confirms that bevacizumab carries serious and potentially life-threatening toxicity risks and emphasizes the importance of early recognition, continuous monitoring, and prompt management of these toxicities. Such toxicities include hemorrhage/bleeding, wound healing complicatons, gastrointestinal perforation, arterial thromboembolism, congestive heart failure, hypertension, proteinuria/nephrotic syndrome, infusion-related hypersensitivity reactions, and reversible posterior leukoencephalopathy syndrome. Patients at the highest risk for these toxicities are individuals with a history of hypertension, thromboembolism, bleeding, cardiovascular disease, or preexisting proteinuria, as these conditions may be exacerbated by bevacizumab use. Additionally, particular tumor types correlate with risk for individual toxicities; for example, patients with squamous non-small-cell lung cancer or rectal cancer have a higher risk of bleeding, those with renal cell carcinoma have a higher proteinuria risk, and patients with colorectal Cancer have a higher risk of gastrointestinal perforation. Further investigation is warranted to develop effective management strategies for these toxicities. CONCLUSIONS: As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities that can arise and to develop practice guidelines for their management.