Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial.

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).

Cardiac safety of (neo)adjuvant trastuzumab in the community setting: a single-center experience.

BACKGROUND: Trastuzumab improves the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). The incidence and long-term impact of trastuzumab-related cardiotoxicity in the community setting is of great clinical importance. MATERIAL AND METHODS: Patients with HER2-positive BC treated with (neo)adjuvant trastuzumab were retrospectively evaluated. Cardiotoxicity was defined as cardiac death or absolute decrease in left ventricular ejection fraction of at least 10% to a value less than 50%, or symptomatic heart failure. RESULTS: We evaluated 237 patients: median age 53 years (range 27-83 years). 40.5% of these patients had received neoadjuvant and 59.5% adjuvant chemotherapy. The majority (83.9%) were treated with an anthracycline-based regimen. Median exposure to trastuzumab was 8 months (range 2-12 months). Cardiotoxicity was diagnosed in 20.2%, but symptoms only occurred in 3.8%. 41.6% recovered cardiac function. None of the risk factors were associated with cardiotoxicity. CONCLUSION: The incidence of trastuzumab-related cardiotoxicity found in this study was slightly higher than those reported in randomized clinical trials. Nevertheless, most patients were asymptomatic. We describe the cardiac outcomes of a non-selected population, which possibly reflects those found in the 'real world'. The risks versus benefits of trastuzumab use remain in favor of treatment, but cardiotoxicity should be monitored.