ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCancer Therapy Related Organ ToxicitiesView all 17 articles
Hepatotoxicity associated with anti-neoplastic agents: a pharmacovigilance analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database
Provisionally accepted
- 1Changzhou First People's Hospital, Changzhou, China
- 2Kangda College of Nanjing Medical University, Lianyungang, China
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Background: Hepatotoxicity is commonly observed in patients undergoing chemotherapy. However, the clinical features and outcomes of hepatotoxicity associated with anti-neoplastic agents remain unclear. In this study, we investigated the characteristics and risk factors of hepatotoxicity associated with anti-neoplastic agents. Methods: We conducted a retrospective pharmacovigilance analysis using data acquired from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024). Hepatotoxicity risk was assessed by disproportionality analysis, while LASSO and multivariate logistic regression were applied to control for potential confounders. Finally, we analyzed the time duration to the onset of hepatotoxicity. Results: A total of 56 anti-neoplastic agents exhibited positive signals for hepatotoxicity, involving 4,195 reports. Female patients (46.50%) were more frequently affected than males (26.70%), with a median age of 56 years. 627 patients (14.95%) experienced fatal or life-threatening outcomes. The top three drugs with the highest Reporting Odds Ratio (ROR) values were mercaptopurine (ROR=26.57), pegaspargase (ROR=13.67) and blinatumomab (ROR=11.93). Most events occurred within the first month (44.18%) and the median TTO value in the Fatal group (22.5 days) was shorter than that in the non-fatal group (42 days) (p<0.05). Furthermore, Weibull shape parameter (WSP) analysis indicated that 20 of the top 30 drugs were random failure models. Conclusion: This analysis profiles hepatotoxicity signals for anti-neoplastic agents but reveals a major methodological gap: without using a validated causality tool like the updated RUCAM, FAERS data cannot confirm drug-induced liver injury (DILI). Future studies should integrate RUCAM to improve specificity and clinical relevance.
Keywords: Anti-neoplastic agents, Disproportionality analysis, FAERS, Hepatotoxicity, Pharmacovigilance
Received: 14 Jul 2025; Accepted: 05 Dec 2025.
Copyright: © 2025 Shi, Wang, Qu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rong Chen
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