Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis

• Published in: Annals of oncology Vol. 20; no. 9; pp. 1535 - 1542
• Main Authors: Di Lorenzo, G., Autorino, R., Bruni, G., Cartenì, G., Ricevuto, E., Tudini, M., Ficorella, C., Romano, C., Aieta, M., Giordano, A., Giuliano, M., Gonnella, A., De Nunzio, C., Rizzo, M., Montesarchio, V., Ewer, M., De Placido, S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-2009; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - adverse effects; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Carcinoma, Renal Cell - complications; Carcinoma, Renal Cell - drug therapy; Cardiology. Vascular system; cardiotoxicity; Coronary Disease - complications; Female; Heart - drug effects; Humans; hypertension; Hypertension - chemically induced; Hypertension - complications; Indoles - adverse effects; Kidney Neoplasms - complications; Kidney Neoplasms - drug therapy; Kidneys; Male; Medical sciences; metastatic kidney cancer; Middle Aged; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Pyrroles - adverse effects; Retrospective Studies; Risk Factors; Stroke Volume - drug effects; Sunitinib; Tumors of the urinary system; Ventricular Function, Left - drug effects; sunitinib; cardiotoxicity; metastatic kidney cancer; hypertension; Antineoplastic agent; Carcinoma; Toxicity; Multicenter study; Cardiovascular disease; Metastasis; Sunitinib; Grawitz tumor; Advanced stage; Antiangiogenic agent; Protein-tyrosine kinase; Kidney disease; Hypertension; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Malignant tumor; Treatment; Analysis; Kidney cancer; Multikinase inhibitor; Circulatory system; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdp025

Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent.
The medical records of 175 patients with metastatic RCC treated with sunitinib at eight Italian institutions were retrospectively reviewed. Alterations in left ventricular ejection fraction (LVEF) and blood pressure were evaluated. Patients with preexisting cardiac risk factors were specifically scrutinized for increased expression of cardiac changes.
Grade 3 hypertension was seen in 17 patients (9.7%); in 12 of these 17, hypertension developed after receiving the third sunitinib cycle. Among these 17 patients, 12 (70.6%) also experienced left ventricular systolic (LVEF) dysfunction; in all, 33 of the 175 patients (18.9%) developed some degree of cardiac abnormality, of which 12 were classified as grade 3 LVEF dysfunction and/or congestive heart failure (CHF) (6.9%). Significant univariate associations for predictors of CHF were history of hypertension (P=0.008), history of coronary heart disease (P=0.0005) and prior treatment with an angiotensin-converting enzyme inhibitor (P=0.04). Multivariate analysis suggested that a history of coronary artery disease [odds ratio (OR) 18, 95% confidence interval (CI) 4–160, P=0.005] and hypertension (OR 3, 95% CI 1.5–80, P=0.04) was the only significant independent predictors of CHF.
Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction during treatment.