Pharmacovigilance Insights into Route-Stratified Adverse Events of Platinum-Based Drugs

Platinum-based drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various malignancies. However, the route-stratified adverse-event reporting patterns have not been fully characterized. This study aims to describe and characterize the patterns and time-to-onset distributions of adverse events (AEs) for platinum drugs across intravenous (IV), intraperitoneal (IP), and intraarterial (IA) routes.

Data covering the period from 2004Q1 to 2024Q4 were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analyses were conducted to identify potential safety signals by platinum agent and route. The identified signals were then classified according to clinical priority, a categorization based on clinical relevance, reporting rate, fatality rate, and signal stability. Furthermore, time-to-onset profiles were analyzed using Kaplan-Meier analysis, the log-rank test, and Weibull shape parameter modeling.

The study identified AE reports associated with cisplatin (5,783 IV, 193 IP, 135 IA), carboplatin (17,091 IV, 115 IP, 171 IA), and oxaliplatin (18,845 IV, 170 IP, 108 IA). IP reports were more frequently submitted for female patients, whereas IA reports were more frequently submitted for male patients, likely reflecting route-associated clinical indications. AE reporting profiles differed by platinum agent and route, with partial overlap. Among the identified AEs, twelve AEs were classified as high clinical priority. Of these, hepatic failure was the most frequently reported high-priority AE for both IV cisplatin and IV oxaliplatin. Notably, all IV platinum agents exhibited early failure- type patterns. The cumulative reporting distributions following IV administration differed significantly by drug. Patients treated with cisplatin showed shorter time to onset, with a median of 16 days (IQR: 7-46 days).

Through a comprehensive analysis of FAERS data, this study has identified and characterized the AE signals for platinum drugs across IV, IP, and IA routes, assessed clinical priorities, and elucidated temporal characteristics. These findings should be interpreted as exploratory pharmacovigilance signals because FAERS does not support incidence estimation, comparative risk assessment, or causal inference. Therefore, large-scale prospective studies are warranted to validate and extend these results.

This study identified differences in AE reporting profiles and time-to-onset patterns stratified by platinum agent and administration route. This underscores the importance of pharmacovigilance and the integration of safety monitoring systems to facilitate timely identification and management of AEs in clinical practice.