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.


METHODS
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.


METHODS
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.


RESULTS
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 complications, 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.
Gressett
Sarah M
SM
Veterans Affairs North Texas Health Care System, Dallas, TX 75216, USA.
Shah
Sachin R
SR
D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006333:Heart Failure / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007416:Intestinal Perforation / Q000139:chemically induced; D011507:Proteinuria / Q000139:chemically induced; D013923:Thromboembolism / Q000139:chemically induced; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab