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Annals of Oncology Advance Access published online on April 23, 2008
Annals of Oncology, doi:10.1093/annonc/mdn168
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate

M. L. Telli1, R. M. Witteles2, G. A. Fisher1 and S. Srinivas1,*

1 Division of Medical Oncology, Department of Medicine
2 Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, USA

* Correspondence to: Dr S. Srinivas, Department of Medicine, Division of Medical, Oncology, Stanford University 875 Blake Wilbur Drive, Stanford, CA 94305, USA. Tel: +1-650-725-2078; Fax: +1-650-736-1640; E-mail: sandysri{at}stanford.edu

Background: In the pivotal phase III metastatic renal cell carcinoma trial, updated data indicates that 21% of sunitinib-treated patients experienced a decline in left ventricular ejection fraction to below normal. This cardiotoxicity was reported to be reversible and without clinical sequelae. We conducted a retrospective analysis of our institutional experience of cardiotoxicity with sunitinib after observing a high incidence of symptomatic heart failure.

Patients and methods: Patients receiving sunitinib at Stanford University from 1 July 2004 to 1 July 2007 were identified. Medical records were reviewed and those patients experiencing symptomatic grade 3/4 left ventricular systolic dysfunction were identified. Potential cardiac risk factors were analyzed.

Results: Forty-eight patients treated with sunitinib were assessable. Seven patients experienced symptomatic grade 3/4 left ventricular dysfunction 22–435 days after initiation of sunitinib. Three patients had persistent cardiac dysfunction after discontinuation of sunitinib and initiation of heart failure therapy. A history of congestive heart failure, coronary artery disease and lower body mass index were factors associated with increased risk.

Conclusions: Among patients treated with sunitinib at our institution, 15% developed symptomatic grade 3/4 heart failure. Future studies of sunitinib-related cardiotoxicity are urgently needed, particularly as the oncologic indications for this drug continue to expand.

cardiotoxicity, congestive heart failure, sunitinib, tyrosine kinase inhibitor

Received for publication January 17, 2008. Revision received March 19, 2008. Accepted for publication March 20, 2008.


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