Prevention of Adjuvant Treatment Induced Cardiotoxicity in Egyptian Breast Cancer (BC) Patients: A Randomized Prospective Study
Journal of Cancer and Tumor International,
Background: Adjuvant Anthracyclines Chemotherapy (ANTC) and trastuzumab have been documented to prolong survival in patients with breast cancer (BC). However, these drugs are also well known to induce left ventricular systolic dysfunction (LVSD). Multiple studies have shown that angiotensin converting enzyme inhibitors (ACEIs) and beta blockers (BBs) can prevent LVSD among women with BC.
Objectives: We aimed to prospectively evaluate the efficacy of enalapril (ACEI) and carvedilol (BB) in preventing the ANTC ± trastuzumab induced LVSD, in patients with non-metastatic BC.
Patients and Methods: We randomized 126 patients with non-metastatic (M0) BC, who were scheduled to be treated with ANTC ± trastuzumab into the intervention group (group 1; n = 63), which received enalapril and carvedilol or the control group (group 2; n = 63), which did not receive enalapril or carvedilol. To evaluate left ventricular (LV) systolic and diastolic functions the conventional echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) were performed at baseline, after 3 therapy cycles, and at 1-year follow-up. The secondary endpoint was designed to detect the incidence of a decrease in left ventricular ejection fraction (LVEF) ≥ 10%, heart failure (HF), LVSD (defined as LVEF<45%) or deterioration in LV diastolic function.
Results: In the intervention group, 58 patients had 3 cycles ANTC, 6 patients received 6 cycles ANTC, and 12 patients received trastuzumab. In the control group, 47 patients had 3 cycles ANTC, 16 patients were given 6 cycles ANTC and 18 patients received trastuzumab (as per the guidelines issued by breast clinic in the department of clinical oncology, faculty of medicine, Ain Shams University) for adjuvant and neoadjuvant chemotherapy in early breast cancer).
After 3 ANTC cycles, LVEF did not change in the intervention group, but decreased by M-mode in the control group (p-value: 0.03), which was associated with statistically significant deterioration of LV diastolic function. At 1 year follow-up, while no change was observed in LVEF in group 1, there was a decrease in LVEF by CMR in group 2 (65.78% at baseline, 61.48% at 1 year; p-value: 0.04 8).
Conclusion: Combined prophylaxis with enalapril and carvedilol may prevent LVSD in patients with non-metastatic BC treated with anthracycline-containing chemotherapy ± trastuzumab. However, the clinical relevance of this strategy should be confirmed in the future, large-scale randomized studies.
- breast cancer (BC)
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