Vonica Razvan Constantin, Butuca Anca, Vonica-Tincu Andreea Loredana, Morgovan Claudiu, Pumnea Manuela, Cipaian Remus Calin, Curca Razvan Ovidiu, Batar Florina, Vornicu Vlad, Solomon Adelaida, Frum Adina, Dobrea Carmen Maximiliana, Axente Dan Damian, Gligor Felicia Gabriela
Preclinical Department, Faculty of Medicine, "Lucian Blaga" University of Sibiu, 550169 Sibiu, Romania.
Clinical Department, Faculty of Medicine, "Lucian Blaga" University of Sibiu, 550169 Sibiu, Romania.
Cancers (Basel). 2024 Nov 16;16(22):3847. doi: 10.3390/cancers16223847.
Capecitabine (CAP) is one of the most commonly prescribed fluoropyrimidines in oncology, especially in the treatment of colon cancer. Cardiac toxicity is a severe and potentially lethal adverse drug reaction (ADR) against fluoropyrimidines. Cardiac ADRs, such as myocardial infarction (MI), heart failure (HF), arrhythmias, and a number of cardiomyopathies, are reported for these molecules. To have a better understanding of the risk-benefit ratio of colon cancer therapy, a pharmacovigilance study of real-world evidence of the cardiac toxicity of antineoplastic agents is required.
This post-marketing research on CAP aims to assess the risk of cardiac toxicity. Five other antitumor drugs used in colorectal cancer, i.e., 5-fluorouracil (5-FU), irinotecan (IRI), oxaliplatin (OX), bevacizumab (BEV) and panitumumab (PAN), were also studied to create a relative profile of observed cardiotoxicity.
A retrospective study based on reports submitted in the EudraVigilance (EV) database until 28 July 2024 was conducted. Using the aggregated data from EV, a descriptive analysis and disproportionality analysis of cardiac ADRs induced by fluoropyrimidines were performed. To evaluate the disproportionality of the signals, Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated by comparison with other drugs used in colorectal cancer: 5-FU, IRI, OX, BEV, and PAN.
"Cardiac disorders" represent 3.4% of the total reports for CAP. The value is comparable to 5-FU, but higher than for other drugs. t was observed that there are no significant differences in the occurrence of cardiac ADRs in patients exposed to CAP and 5-FU treatments, and in particular MI and HF. Compared to 5-FU, which could produce cardiac arrythmias with a higher probability than all other drugs, CAP has a higher probability of reporting this ADR only in comparison with IRI (ROR: 1.2971; 95% CI: 1.0196-1.6502).
CAP induces adverse cardiovascular reactions, especially MI, HF, and cardiomyopathies. Arrhythmias have been shown to be side effects more frequent associated with 5-FU than with CAP. The results emphasize the need for a rigorous cardiovascular monitoring of patients following treatment with CAP or 5-FU and especially for those with pre-existing cardiac pathology.
卡培他滨（CAP）是肿瘤学中最常用的氟嘧啶类药物之一，尤其用于治疗结肠癌。心脏毒性是氟嘧啶类药物严重且可能致命的药物不良反应（ADR）。已报道这些药物会引发心脏ADR，如心肌梗死（MI）、心力衰竭（HF）、心律失常以及多种心肌病。为了更好地了解结肠癌治疗的风险效益比，需要对抗肿瘤药物心脏毒性的真实世界证据进行药物警戒研究。
这项关于卡培他滨的上市后研究旨在评估心脏毒性风险。还对用于结直肠癌的其他五种抗肿瘤药物，即5-氟尿嘧啶（5-FU）、伊立替康（IRI）、奥沙利铂（OX）、贝伐单抗（BEV）和帕尼单抗（PAN）进行了研究，以建立观察到的心脏毒性的相对概况。
基于截至2024年7月28日在欧洲药物警戒数据库（EudraVigilance，EV）中提交的报告进行回顾性研究。利用EV的汇总数据，对氟嘧啶类药物引起的心脏ADR进行描述性分析和不成比例性分析。为评估信号的不成比例性，通过与用于结直肠癌的其他药物：5-FU、IRI、OX、BEV和PAN进行比较，计算报告比值比（ROR）和95%置信区间（95%CI）。
“心脏疾病”占卡培他滨总报告的3.4%。该值与5-FU相当，但高于其他药物。观察到接受卡培他滨和5-FU治疗的患者发生心脏ADR的情况，特别是MI和HF，没有显著差异。与5-FU相比，5-FU产生心脏心律失常的概率高于所有其他药物，卡培他滨仅与IRI相比报告这种ADR的概率更高（ROR：1.2971；95%CI：1.0196 - 1.6502）。
卡培他滨会引发不良心血管反应，尤其是MI、HF和心肌病。已表明心律失常是与5-FU相关的比与卡培他滨相关更常见的副作用。结果强调了对接受卡培他滨或5-FU治疗的患者，尤其是有心脏基础疾病的患者进行严格心血管监测的必要性。
