title: Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis.
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.
  
  
  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.
authors.affiliation: Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli. Electronic address: giuseppedilorenzoncol@hotmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Clinica Urologica, Seconda Università degli Studi, Napoli.
authors.forename: R
authors.initials: R
authors.lastname: Autorino
authors.affiliation: UOC Oncologia, INT Fondazione 'G. Pascale', Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Bruni
authors.affiliation: UOC Oncologia, Ospedale Cardarelli, Napoli.
authors.forename: G
authors.initials: G
authors.lastname: Cartenì
authors.affiliation: UO Oncologia, Università Dell'Aquila, L'Aquila.
authors.forename: E
authors.initials: E
authors.lastname: Ricevuto
authors.affiliation: UO Oncologia, Università Dell'Aquila, L'Aquila.
authors.forename: M
authors.initials: M
authors.lastname: Tudini
authors.affiliation: UO Oncologia, Università Dell'Aquila, L'Aquila.
authors.forename: C
authors.initials: C
authors.lastname: Ficorella
authors.affiliation: UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza.
authors.forename: C
authors.initials: C
authors.lastname: Romano
authors.affiliation: UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza.
authors.forename: M
authors.initials: M
authors.lastname: Aieta
authors.affiliation: Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
authors.forename: A
authors.initials: A
authors.lastname: Gonnella
authors.affiliation: UOC Urologia, Ospedale Sant'Andrea, Roma.
authors.forename: C
authors.initials: C
authors.lastname: De Nunzio
authors.affiliation: UOC Oncologia, Ospedale Cardarelli, Napoli.
authors.forename: M
authors.initials: M
authors.lastname: Rizzo
authors.affiliation: UO Oncologia, AO 'Cotugno', Napoli, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Montesarchio
authors.affiliation: Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ewer
authors.affiliation: Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
authors.forename: S
authors.initials: S
authors.lastname: De Placido
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy*; D003327:Coronary Disease / Q000150:complications; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D000077210:Sunitinib; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib