Antineoplastic agent-induced palmar-plantar erythrodysaesthesia syndrome: insights from the FDA adverse event reporting system

Abstract

Palmar-plantar erythrodysaesthesia syndrome (PPE), also called hand-foot syndrome (HFS), is a common cutaneous adverse reaction to anticancer drugs that impairs patients’ quality of life. This study analyzed PPE reports from the U.S. FDA Adverse Event Reporting System (FAERS) to identify associated drugs and characterize their risk profiles. Data from FAERS (2004Q1–2025Q1) were extracted, with duplicates removed. Disproportionality analysis (ROR, PRR, BCPNN, MGPS) was used to identify PPE-associated drugs; time to PPE onset and sex/gender distribution were also analyzed. A total of 21,556 PPE cases involving 427 drugs were identified. Protein kinase inhibitors and antimetabolites were the main drug classes, with regorafenib, sorafenib, and capecitabine showing the strongest signals. Most cases (83.4%) occurred within 90 days of treatment; lapatinib and capecitabine had stronger PPE signals in female patients. The findings highlight the diversity of PPE-associated drugs and the need for monitoring PPE across anticancer therapies. Early PPE onset emphasizes proactive patient education and initial-phase monitoring; Sex/gender-related differences in reporting patterns were observed for several drugs; however, these differences may reflect both disease-related prescribing patterns and potential biological factors and should therefore be interpreted cautiously. This study confirms associations between many antineoplastic agents and PPE, reinforcing the need for enhanced clinical vigilance and tailored monitoring. Further research is needed to elucidate mechanisms and optimize PPE management.