Cardiovascular Side Effects

1Therapies that attack a tumor’s blood supply (antiangiogenesis) are transforming the treatment of cancers of the liver, kidney, and gastrointestinal tract, among others. Antiangiogenic agents target the blood supply to tumors, primarily by blocking the actions of angiogenic growth factors and their signaling pathways. VEGF (vascular endothelial growth factor) and PDGFR (platelet-derived growth factor receptor) were the first validated angiogenic targets, but many others are being targeted by newer therapies. Bevacizumab (BV; Avastin®), the first specifically designed antiangiogenic cancer agent, is a humanized monoclonal antibody that binds circulating VEGF, thus preventing the ligand from acting on the receptor. Two other approved agents, sorafenib (Nexavar®) and sunitinib (Sutent®), are orally administered small molecule tyrosine kinase inhibitors (TKIs) that disrupt intracellular angiogenic signaling by binding competitively to the ATP binding sites on receptors for VEGF and other growth factors. Antiangiogenic therapies are generally well tolerated compared to traditional cytotoxic chemotherapy agents, primarily because they are more selective in their cellular effects. Nonetheless, they are associated with a variety of distinct side effects that require monitoring and management. The TKIs cause a wider range of side effects than antibody therapy due to their broader activity beyond angiogenesis inhibition. In clinical trials of sunitinib, the most frequently reported toxicities were diarrhea, hypertension, fatigue, and nausea, while for sorafenib they were diarrhea, skin toxicities, and alopecia1. BV is most often associated with hypertension and proteinuria (excess protein in the urine), followed by mild thrombotic and bleeding events. Other notable but infrequent side effects with BV therapy include serious (grade 3-4) bleeding, arterial thromboembolism, wound healing complications, GI perforation, and nephrotic syndrome2. This article reviews the major classes of side effects of antiangiogenic therapies and their management