Neurotoxic Signals of 14 Chemotherapeutic Agents: Global Real-World Evidence and Nursing Implications Based on FAERS and EudraVigilance Databases

Abstract

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating dose-limiting toxicity. Despite its clinical significance, real-world data integrating long-term temporal dynamics with specific nursing care strategies remain limited. This study aims to characterize CIPN signals and onset patterns to provide evidence-based guidance for oncology nursing.

Methods: We performed a retrospective analysis of the US FDA Adverse Event Reporting System (FAERS, 2004–2025), with parallel validation using the EudraVigilance database (EV, 2003–2025). Disproportionality was assessed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Empirical Bayes Geometric Mean (EBGM) for 14 chemotherapeutic agents. Time-to-Onset (TTO) and clinical severity were evaluated to identify high-risk periods and vulnerable subpopulations.

Results: A total of 9,078 reports were identified in FAERS, with 10,056 reports from EV providing a robust external validation. Both datasets showed a high level of clinical fidelity, with 94.56% of EV reports originating from healthcare professionals. Females and patients aged ≥45 were most affected. In FAERS, the median TTO was 25 days (IQR: 6–78 days), with 54.50% of cases manifesting within the first month. Vincristine showed the highest signal intensity in FAERS (ROR: 12.90), while Paclitaxel (ROR: 7.83) and Vincristine (ROR: 5.04) dominated the EV dataset. Granular PT analysis in EV further confirmed high-intensity signals for peripheral sensory neuropathy (ROR: 9.26) and polyneuropathy (ROR: 20.01). Fatal outcomes in FAERS were associated with a significantly longer TTO (32 days) compared to non-fatal cases (P=0.0288).

Conclusions: CIPN is a predominantly early-onset, severe toxicity requiring immediate vigilance during the first chemotherapy cycle. Nursing interventions must transition from reactive management to proactive, agent-specific monitoring and longitudinal education.