Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate.
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.


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.
Telli
M L
ML
Division of Medical Oncology, Department of Medicine, Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
Witteles
R M
RM
Fisher
G A
GA
Srinivas
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D013318:Stroke Volume / Q000187:drug effects; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000453:epidemiology
D007211:Indoles; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib