Bevacizumab-related toxicities: association of hypertension and proteinuria

Cynthia L. Martel, MD, PhD, Cary A. Presant, MD, FACP, Ben Ebrahimi, MD, Gargi Upadhyaya, MD, Mayank Vakil, MD, Christina Yeon, MD, Linda D. Bosserman, MD, FACP, and Richard Horns, MD

City of Hope Medical Group, Pasadena, CA, and Wilshire Oncology Medical Group, La Verne, CA

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has demonstrated clinical activity in colorectal, renal, breast, and lung cancers. It has been associated with hypertension, proteinuria, and other unique toxicities. We examined the incidence and management of bevacizumab-related toxicities since the US Food and Drug Administration approved the drug in 2004. Forty consecutive patients receiving bevacizumab were evaluated. New or worsened hypertension developed in 12 patients (30%), and proteinuria occurred in 9 patients (23%), 6 of whom also developed hypertension. Bevacizumab was stopped in two patients due to proteinuria and was temporarily or permanently withheld in four patients due to other toxicities (perforated nasal septum, fissure, gastrointestinal bleeding, and chest pain). The total incidence of toxicity was 47.5%. There was a statistically significant association between hypertension and proteinuria (P = 0.006). Fifteen percent of patients developed a syndrome of proteinuria and hypertension, which we have termed BETS (bevacizumab toxicity syndrome). Since hypertension and proteinuria are statistically associated, we suggest that optimal management of BETS should include early intervention with antihypertensive drugs protective against proteinuria and nephropathy, such as angiotensin-converting enzyme inhibitors. Prompt intervention before hypertension or proteinuria becomes severe may allow prolonged therapy with bevacizumab and, therefore, improved clinical outcomes.

Commun Oncol 2006;3:90–93 print e-mail full text 82 kb