儿科患者抗癌药物的心脏毒性：来自世卫组织药物警戒数据库的见解

IF 2.2 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Archives of Cardiovascular Diseases Pub Date : 2025-09-01 DOI:10.1016/j.acvd.2025.06.017

Fabien Labombarda , Jérémie Rouger , Damien Legallois , Joachim Alexandre , Basile Chrétien

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引用次数: 0

摘要

与抗癌药物相关的心血管毒性是儿科癌症患者治疗的主要问题。在心肌毒性高风险的特定人群中，关于急性癌症治疗相关心功能障碍（CTRCD）负担的可靠数据很少。使用世界卫生组织个案安全报告数据库VigiBase®，我们旨在确定抗癌药物与儿童急性CTRCD之间的关系。方法对VigiBase®中249种FDA或ema标记的抗癌药物进行歧化分析，评估CTRCD报告的多变量调整报告奇比（aROR）及其95%置信区间（CI），然后对VigiBase®中鉴定的抗癌药物的CTRCD发病时间进行描述性分析。结果在VigiBase®中，共有796例CTRCD病例与至少一种抗癌药物相关。在对整个儿科人群的多变量分析中，16种抗癌药物与CTRCD报告显著相关，其中10种（63%）主要用于血液系统恶性肿瘤，2种是以前未报道的新的CTRCD关联，包括拓扑异构酶1抑制剂（Topotecan）和细胞毒抗生素（Dactinomycine）（图1）。结论：我们在Vigibase®中发现16种抗癌药物与儿科CTRCD报告显著相关。我们的分析证实了之前在儿童中广泛报道的一些关联（如蒽环类药物），并发现了新的信号，如全身性暴露于拓扑替康和放线菌素。现在需要专门的前瞻性临床试验来证实这些结果。

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Cardiotoxicity of Anticancer Drugs in Pediatric Patients: Insights from the WHO Pharmacovigilance Database

Introduction

Cardiovascular toxicities associated with anticancer drugs are a major problem for pediatric patients treated for cancer. Reliable data concerning the burden of acute cancer-therapy related cardiac dysfunction (CTRCD) are scarce in this specific population at high risk of myocardial toxicity. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and acute CTRCD in children.

Method

A disproportionality analysis evaluating the multivariable adjusted reporting odd-ratios (aROR) for CTRCD reporting with their 95% confidence intervals (CI) was performed for 249 FDA- or EMA-labeled anticancer drugs in VigiBase® in 4 pediatric age classes (0–27 days, 28 days–23 months, 2–11 years, 12–17 years), followed by a descriptive analysis of the time to CTRCD onset for the anticancer drugs identified in VigiBase®.

Results

A total of 796 CTRCD cases associated with at least one anticancer drug were identified in VigiBase® In the multivariate analysis on the whole pediatric population, 16 anticancer drugs were significantly associated with CTRCD reporting of which 10 (63%) are mainly used in hematologic malignancies and 2 represented new CTRCD associations not previously reported in literature including topo-isomerase 1 inhibitor (Topotecan) and cytotoxics antibiobics (Dactinomycine) (Figure 1).

Conclusion

We identified in Vigibase® 16 anticancer drugs significantly associated with CTRCD reporting in pediatrics. Our analysis confirmed some of associations that were extensively previously reported in children (as for anthracyclines), and found new signals such as systemic exposure to Topotecan and Dactinomycin. Dedicated prospective clinical trials are now required to confirm these results.

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来源期刊

Archives of Cardiovascular Diseases 医学-心血管系统

CiteScore

4.40

自引率

6.70%

发文量

审稿时长

34 days

期刊介绍： The Journal publishes original peer-reviewed clinical and research articles, epidemiological studies, new methodological clinical approaches, review articles and editorials. Topics covered include coronary artery and valve diseases, interventional and pediatric cardiology, cardiovascular surgery, cardiomyopathy and heart failure, arrhythmias and stimulation, cardiovascular imaging, vascular medicine and hypertension, epidemiology and risk factors, and large multicenter studies. Archives of Cardiovascular Diseases also publishes abstracts of papers presented at the annual sessions of the Journées Européennes de la Société Française de Cardiologie and the guidelines edited by the French Society of Cardiology.