title: Sunitinib, hypertension, and heart failure: a model for kinase inhibitor-mediated cardiotoxicity.
abstract: 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.
authors.affiliation: Division of Cardiology and Feinberg Cardiovascular Research Institute, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA. rgupta@northwestern.edu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Gupta
authors.forename: Michael L
authors.initials: ML
authors.lastname: Maitland
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D007211:Indoles / Q000009:adverse effects*; D032383:Myocytes, Cardiac; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000009:adverse effects*; D012307:Risk Factors; D000077210:Sunitinib; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib