Sunitinib, Hypertension, and Heart Failure: A Model for Kinase Inhibitor-Mediated Cardiotoxicity

Kinase inhibitors have emerged as an important new class of agents for the treatment of diverse tumors. Sunitinib malate is a small-molecule, oral, multi-kinase inhibitor approved for use in treating renal cell carcinoma and gastrointestinal stromal tumor. It has also demonstrated efficacy in treating pancreatic neuroendocrine tumors and is being evaluated for the treatment of other cancers. Initially developed for its inhibition of the vascular endothelial growth factor (VEGF) signaling pathway, sunitinib has been associated with hypertension and heart failure. This review examines the incidence and severity of these adverse events, relevant findings from other agents that inhibit VEGF signaling, the mechanisms underlying these effects, and suggestions for their clinical management. Hypertension is a common adverse effect that is usually easily managed. The associated heart failure is less common; it can be reversible but must be actively monitored and managed. Mechanistic insights suggest that an attentive clinical strategy for hypertension could prevent severe cardiotoxicity.