Cardiovascular Effects of Sunitinib Therapy (CREST)

Renal Cell Carcinoma 4

Tyrosine kinase inhibitors such as sunitinib are used in the treatment of renal cell carcinoma and have significant off-target effects with cardiac toxicity and resultant ventricular cardiac dysfunction being a major concern. However, the mechanisms of these effects in humans remains poorly defined, as are the clinical methods to risk stratify and identify patients who will ultimately suffer from cardiac dysfunction. The goal of this multi-center study is to characterize the cardiovascular measures of cardiac function; 2) comprehensive measures of arterial function and left ventricular afterload; 3) biomarkers reflective of the pathophysiologic alterations. Through this work, the investigators will translate our basic understanding of sunitinib cardiotoxicity to humans and identify early predictors of sunitinib cardiotoxicity.

Tyrosine kinase inhibitors such as sunitinib have dramatically improved the overall management of certaincancers including renal cell carcinoma. However, recent data suggest that these therapieshave significant off-target effects with cardiac toxicity, including significant hypertension and ventricular cardiac dysfunction being a major concern. However, the biologic mechanisms underlying cardiotoxicty in humans remain poorly defined. Moreover, there is a critical need to develop methods to improve the risk stratification and early identification of patients who will suffer from hypertension and cardiac dysfunction with exposure to therapy. The over all objectives ofthis study are to further characterize the cardiovascular changes that occur with sunitinib exposure in order to improve our understanding of sunitib toxicity and determine early, mechanistically and clinically relevant predictors to identify patients at increased risk of hyptertension and cardiac dysfunction. The specific aims of this study are: 1) To define the changes in arterial hemodynamics that may occur with exposure to sunitinib, 2) To define the changes in sensitive echocardiographic measures of cardiac function that may occur with exposure to sunitinib, 3) To determine blood markers that are associated with changes in vasculature or cardiac function with exposure to sunitinib. and 4) To determine if there are early imaging or biomarker predictors of subitinib cardiotoxicity.

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