Hypertension and cardiotoxicity in metastatic renal cell carcinoma (mRCC) treated with sunitinib (SU).

Abstract

e15073 Background: Recent data have shown that cardiotoxicity (CHFcongestive heart failure, CADcoronary artery disease)could be an important side-effect in patients (pts) with RCC treated with tyrosine kinase inhibitors (TKIs). LVEF(Left ventricular ejection fraction)reduction may occur in up to 10% of pts treated with SU and uncontrolled hypertension could worse this side-effect. This complication is reversible with TKI interruption and appropriate antihypertensive therapy. Methods: We have prospectively analyzed patients receiving SU as a first-line treatment for mRCC. Between April 2007 and December 2011,31 consecutive pts, median age 67 yrs (41-80) were treated with SU at the standard dose of 50 mg/day,4 weeks on and 2 weeks off. We recorded for all pts CAD risk factors, preexisting hypertension,rhythm disturbances and heart failure. ECG, echocardiography and cardiology consultation were performed at baseline, and every three months until progression or permanent SU discontinuation. We searched correlations between cardiotoxicity onset and hypertension. Results were assessed with paired Student’s t-test and Chi-square test. Results: At baseline,we found 22 pts (71%) with hypertensive disease (HD). The median duration treatment was 8,3 months(22-0,4).On TKI therapy 6/22 pts (27.2%) worsened the preexisting HD, which was controlled with adequate treatment according to American Heart Association guidelines, without determining treatment discontinuation. Furthermore 6/31 pts (19%) developed this adverse event. In 14/31 pts (45%) we showed a median ≥ 10% LVEF reduction compared to baseline value (p=.001); 13/31 pts were asymptomatic and only one presented symptoms of CHF and discontinued the treatment. In this study, history of HD,worsening of preexisting HD or development of HD are not predictive for >10% LVEF reduction (p=ns). Conclusions: In pts with mRCC receiving SU as a first-line treatment, HD is not predictive for LVEF reduction. Moreover on TKI therapy there is a statistically significant LVEF reduction, but this adverse event does not determine a treatment discontinuation. A cardiovascular monitoring during SU treatment may reduce this event in order to allow an adequate treatment.