title: The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients.
abstract: OBJECTIVE
  The purpose of this study was to document the incidence and extent of cardiovascular toxicity among advanced renal cell carcinoma patients treated with newer targeted cancer agents.
  
  
  BACKGROUND
  The potential for targeted cancer agents to induce cardiovascular toxicity has been increasingly recognized, but the overall incidence and extent of toxicity have not been well characterized. Early detection of asymptomatic patients could preempt symptomatic toxicity and reduce treatment-related morbidity and mortality.
  
  
  METHODS
  The incidence of hypertension, left ventricular dysfunction, and heart failure was assessed for all advanced renal cell carcinoma patients treated with targeted therapies at our institution between 2004 and 2011. Grading was performed according to the Common Terminology Criteria for Adverse Events version 4.0.
  
  
  RESULTS
  Cardiovascular toxicity developed in 116 of 159 patients (73%), including 52 of 159 patients (33%) when hypertension was excluded. Toxicity varied from occurrences of asymptomatic drops in left ventricular ejection fraction to rises in N-terminal-pro-B-type natriuretic peptide to severe heart failure. The tyrosine kinase inhibitor sunitinib was the agent most frequently used, with 66 of 101 sunitinib-treated patients (65%) developing a form of cardiovascular toxicity, including 32 of 101 patients (32%), excluding hypertension. Other VEGF inhibitors such as bevacizumab, sorafenib, and pazopanib also elicited significant cardiovascular toxicity with incidences ranging from 51% to 68%.
  
  
  CONCLUSIONS
  The frequency and severity of cardiovascular toxicity in advanced renal cell carcinoma patients treated with targeted cancer therapies are high.
authors.affiliation: Department of Internal Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Hall
authors.affiliation: Division of Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.affiliation: Division of Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: witteles@stanford.edu.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Witteles
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D011505:Protein-Tyrosine Kinases
keywords: chemotherapy; heart failure; hypertension; tyrosine kinase inhibitor