Related Experiment Video
Updated: May 10, 2025
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Identification of Anticancer Drugs Associated With Cancer Therapy-Related Cardiac Dysfunction in Pediatrics-Analysis
Fabien Labombarda1, Jérémie Rouger2,3, Damien Legallois4,5
1Department of Cardiology, Normandie University, UNICAEN, CHU Caen-Normandie, Caen, France.
Aims:
Cardiovascular toxicities associated with anticancer drugs constitute a significant concern for pediatric patients undergoing cancer treatment. Comprehensive data on the burden of cancer therapy-related cardiac dysfunction (CTRCD) are lacking, particularly for this high-risk population susceptible to develop myocardial toxicity. By analyzing VigiBase, the World Health Organization's individual case safety report database, we sought to determine anticancer drugs associated with CTRCD in pediatric patients.
Methods And Results:
To evaluate the association between 249 anticancer drugs labeled by the FDA or EMA and CTRCD reporting, we performed a disproportionality analysis, calculating multivariable adjusted reporting odds ratios (aROR) with their 95% confidence intervals (CI) across four pediatric age classes (0-27 days, 28 days to 23 months, 2-11 years, 12-17 years); ClinicalTrial registration number: NCT05602103. We identified 796 cases of CTRCD associated with at least one anticancer drug in VigiBase. Multivariate analysis across the pediatric age spectrum revealed 16 anticancer drugs significantly associated with CTRCD, of which 10 (63%) are primarily used for hematologic malignancies. Two drugs, a topoisomerase 1 inhibitor (topotecan) and cytotoxic antibiotics (dactinomycin), represented novel associations with CTRCD not previously documented in the literature.
Conclusion:
Within VigiBase, we pinpointed 16 anticancer drugs significantly associated with CTRCD reporting in pediatrics. Our research validated several associations already thoroughly reported in children (such as with anthracyclines), and unveiled novel signals for systemic exposure to topotecan and dactinomycin. The relevance of these findings, especially considering the frequency of co-administration of agents and the lack of information regarding radiation exposure and chemotherapy dosage, would need to be evaluated in the context of clinical trials that use or have used these agents.
Insights
This study identified 16 anticancer drugs linked to cancer therapy-related cardiac dysfunction (CTRCD) in pediatric patients. Novel associations were found for topotecan and dactinomycin, highlighting potential risks in young cancer patients.
Area of Science:
- Pediatric Oncology
- Cardiovascular Toxicology
- Pharmacovigilance
Background:
- Anticancer drugs can cause cardiovascular toxicities in pediatric patients.
- Data on cancer therapy-related cardiac dysfunction (CTRCD) in children is limited.
- Pediatric patients are a high-risk population for myocardial toxicity.
Purpose of the Study:
- To identify anticancer drugs associated with CTRCD in pediatric patients.
- To analyze the World Health Organization's VigiBase for CTRCD reports.
- To determine novel drug-associated CTRCD signals in children.
Main Methods:
- Disproportionality analysis of 249 FDA/EMA-labeled anticancer drugs.
- Utilized VigiBase, the WHO's individual case safety report database.
- Multivariable adjusted reporting odds ratios (aROR) calculated across four pediatric age groups.
Main Results:
- Identified 796 cases of CTRCD associated with anticancer drugs.
- Found 16 anticancer drugs significantly associated with CTRCD in pediatrics.
- Topotecan and dactinomycin showed novel associations with CTRCD.
Conclusions:
- 16 anticancer drugs are significantly associated with CTRCD reporting in pediatric patients.
- Confirmed known associations (e.g., anthracyclines) and identified new signals for topotecan and dactinomycin.
- Further clinical trial evaluation is needed to contextualize findings, considering co-administration and dosage information.
More Related Videos
04:48Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
08:03Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
Published on: October 20, 2022
Related Concept Videos
01:26Heart Failure Drugs: Inotropic Agents
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System