Dewidar Hagar K, Ghannam Amr A, Mostafa Tarek M
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Clinical Oncology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 3. doi: 10.1007/s00210-025-04326-1.
Doxorubicin-induced cardiotoxicity (DIC) is a serious condition that limits its use. Thus, this study aimed at evaluating the efficacy and safety of fenofibrate in attenuating DIC in patients with breast cancer. In this randomized controlled parallel study, 44 patients with stage II and/or stage III breast cancer were randomly allocated into two groups: group 1 (control group; n = 22) which received doxorubicin/cyclophosphamide (AC regimen) for four cycles (cycle is every 3 weeks) and group 2 (fenofibrate group; n = 22) which received AC regimen for four cycles (cycle is every 3 weeks) plus 160 mg of oral fenofibrate 24 h prior to the first cycle of chemotherapy and then once daily until the end of the four chemotherapy cycles. At baseline and after the fourth chemotherapy cycle, all participants were submitted to echocardiography (echo) to evaluate left ventricular ejection fraction (LVEF) and blood sample collection to assess the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), myeloperoxidase (MPO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Data was analyzed using paired and unpaired t-tests, chi-square test, and Fisher exact test. Compared to baseline, the control group (AC) produced a significant increase in the serum levels of both NT-proBNP (P = 0.004) and MPO (P < 0.001). At the end of the study and as compared to the control group, the fenofibrate group showed significantly higher LVEF (P = 0.048) and a lower incidence of cardiotoxicity (P = 0.036). Additionally, the fenofibrate group showed a significant decline in the serum levels of NT-proBNP (P < 0.001) and MPO (P < 0.001). Moreover, fenofibrate was safe and well-tolerated and did not provoke a significant elevation in liver enzymes (P > 0.05). Fenofibrate could represent a promising prophylactic therapy against doxorubicin-induced cardiotoxicity. Trial registration: ClinicalTrials.gov ID: NCT06155331. Trial registration date 1-12-2023.
多柔比星诱导的心脏毒性（DIC）是一种严重的情况，限制了其使用。因此，本研究旨在评估非诺贝特在减轻乳腺癌患者DIC方面的疗效和安全性。在这项随机对照平行研究中，44例II期和/或III期乳腺癌患者被随机分为两组：第1组（对照组；n = 22）接受多柔比星/环磷酰胺（AC方案）四个周期（每3周为一个周期），第2组（非诺贝特组；n = 22）接受AC方案四个周期（每3周为一个周期），并在化疗第一个周期前24小时口服160毫克非诺贝特，然后每天一次，直至四个化疗周期结束。在基线和第四个化疗周期后，所有参与者均接受超声心动图（echo）检查以评估左心室射血分数（LVEF），并采集血样以评估血清N末端B型利钠肽原（NT-proBNP）、髓过氧化物酶（MPO）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平。数据采用配对和非配对t检验、卡方检验和Fisher精确检验进行分析。与基线相比，对照组（AC）的NT-proBNP（P = 0.004）和MPO（P < 0.001）血清水平均显著升高。在研究结束时，与对照组相比，非诺贝特组的LVEF显著更高（P = 0.048），心脏毒性发生率更低（P = 0.036）。此外，非诺贝特组的NT-proBNP（P < 0.001）和MPO（P < 0.001）血清水平显著下降。此外，非诺贝特安全且耐受性良好，未引起肝酶显著升高（P > 0.05）。非诺贝特可能是一种有前景的预防多柔比星诱导的心脏毒性的疗法。试验注册：ClinicalTrials.gov标识符：NCT06155331。试验注册日期：2023年12月1日。
