Efficacy of Treatment With Carvedilol in Preventing Early-Stage Left Ventricular Dysfunction in Patients With Breast Cancer Candidated to Receive Trastuzumab Using 2D Speckle-Tracking Echocardiography

Abstract

Background: Treatment-induced cardiotoxicity is one of the major side effects of trastuzumab<br />treatment in patients with breast cancer. Left ventricular (LV) dysfunction is the leading cause<br />of treatment-induced cardiotoxicity. The development of treatment-induced cardiotoxicity<br />during cancer treatment may force patients to modify or quit the treatment. In this trial, we<br />evaluated the prophylactic effects of carvedilol on LV dysfunction in patients with breast cancer<br />receiving trastuzumab using 2D speckle-tracking echocardiography (2DSTE).<br />Methods: We conducted an open-label randomized clinical trial and enrolled 71 non-metastatic HER-2<br />positive patients with breast cancer candidated to receive trastuzumab. Carvedilol was<br />administered concomitantly with the trastuzumab standard regimen at a dosage of 6.25 mg<br />twice a day and up-titrated to the maximum tolerated dosage. The 2DSTE parameters to<br />evaluate the LV systolic and diastolic functions were evaluated initially and 3 months<br />thereafter.<br />Results: Thirty-six patients were randomly assigned to the carvedilol group and 35 patients to the<br />control group. The mean left ventricular ejection fraction (LVEF) was not significantly different<br />either in both groups or between the 2 groups (P=.61) during the follow-up. In contrast, the<br />global longitudinal strain of the LV (GLS) (P=.000) and the strain rate of the LV systolic<br />function (SRS) (P=.004) as markers of the LV systolic function were reduced in the control<br />group. Furthermore, the LV strain rate of the early (SRE) and late (SRA) diastolic functions<br />were preserved in the patients who received prophylactic carvedilol (P=.000 and P=.005,<br />respectively).<br />Conclusions: Concomitant carvedilol treatment with a maximum tolerable dose in patients with nonmetastatic HER2-positive breast cancer under treatment with trastuzumab might be effective on<br />the reduction of systolic and diastolic echocardiographic findings other than the LVEF in<br />patients with weak markers of heart failure.