Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis.
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.
Di Lorenzo
G
G
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli. Electronic address: giuseppedilorenzoncol@hotmail.com.
Autorino
R
R
Clinica Urologica, Seconda Università degli Studi, Napoli.
Bruni
G
G
UOC Oncologia, INT Fondazione 'G. Pascale', Napoli.
Cartenì
G
G
UOC Oncologia, Ospedale Cardarelli, Napoli.
Ricevuto
E
E
UO Oncologia, Università Dell'Aquila, L'Aquila.
Tudini
M
M
UO Oncologia, Università Dell'Aquila, L'Aquila.
Ficorella
C
C
UO Oncologia, Università Dell'Aquila, L'Aquila.
Romano
C
C
UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza.
Aieta
M
M
UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza.
Giordano
A
A
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
Giuliano
M
M
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
Gonnella
A
A
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
De Nunzio
C
C
UOC Urologia, Ospedale Sant'Andrea, Roma.
Rizzo
M
M
UOC Oncologia, Ospedale Cardarelli, Napoli.
Montesarchio
V
V
UO Oncologia, AO 'Cotugno', Napoli, Italy.
Ewer
M
M
Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
De Placido
S
S
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli.
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
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib