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

Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis G. Di Lorenzo1,*, R. Autorino2, G. Bruni3, G. Cartenì4, E. Ricevuto5, M. Tudini5, C. Ficorella5, C. Romano6, M. Aieta6, A. Giordano1, M. Giuliano1, A. Gonnella1, C. De Nunzio7, M. Rizzo4, V. Montesarchio8, M. Ewer9 and S. De Placido1 + Author Affiliations 1Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli 2Clinica Urologica, Seconda Università degli Studi, Napoli 3UOC Oncologia, INT Fondazione ‘G. Pascale’, Napoli 4UOC Oncologia, Ospedale Cardarelli, Napoli 5UO Oncologia, Università Dell'Aquila, L'Aquila 6UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza 7UOC Urologia, Ospedale Sant'Andrea, Roma 8UO Oncologia, AO ‘Cotugno’, Napoli, Italy 9Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA *Correspondence to: Dr G. Di Lorenzo, Dipartimento di Endocrinologia e Oncologia Clinica e Molecolare, Università Federico II, Napoli, Italy. Tel: +39-081-7463660; Fax: +39-081-8997370; E-mail: giuseppedilorenzoncol@hotmail.com Received November 4, 2008. Revision received December 18, 2008. Accepted January 19, 2009. Abstract Background: 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. Patients and methods: 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. Results: 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. Conclusions: 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. Key words cardiotoxicityhypertensionmetastatic