Comprehensive pharmacovigilance of phytoalkaloid chemotherapeutics: Signal detection and time-to-onset analysis based on FAERS

Plant alkaloid-based chemotherapeutic agents, including paclitaxel, vincristine, and irinotecan, play a crucial role in cancer treatment. However, their use is frequently associated with adverse drug events (ADEs), which can impact patient safety and treatment outcomes. Despite prior research, there is still a lack of comprehensive real-world data analysis to systematically investigate ADEs associated with these drugs. This study extracted ADE reports related to paclitaxel, vincristine, and irinotecan from the FDA Adverse Event Reporting System (FAERS) database up to Q4 2024. Data processing was conducted using MySQL and Statistical Analysis System software, and adverse events (AEs) were categorized based on the Medical Dictionary for Regulatory Activities (MedDRA) classification system. Disproportionality analysis was employed using 4 methodologies - reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and Multi-Item Gamma Poisson Shrinker (MGPS) - to detect statistically significant safety signals. Additionally, Weibull survival analysis was conducted to evaluate the time-to-onset distribution of ADEs, allowing for a deeper understanding of the temporal patterns of adverse reactions. A total of 31,007, 7389, and 12,049 ADE reports were retrieved for paclitaxel, vincristine, and irinotecan, respectively. Disproportionality analysis identified significant ADE signals across 27 system organ classes, with the most frequently reported AEs involving hematologic, gastrointestinal, neurological, and hepatic disorders. Novel ADE signals were detected for each drug: paclitaxel (10 new signals), vincristine (10 new signals), and irinotecan (8 new signals). Representative newly identified ADEs include dyspnea, flushing, and back pain for paclitaxel, febrile neutropenia, pancytopenia, and sepsis for vincristine, and neuropathy peripheral, malignant neoplasm progression, and pulmonary embolism for irinotecan. Time-to-onset analysis indicated that ADE occurrences predominantly peaked within the first 30 days of treatment, following an early failure pattern, suggesting that intensive monitoring during this period may be necessary. This study provides a comprehensive real-world safety evaluation of plant alkaloid-based chemotherapeutic agents, identifying both known and previously unreported ADEs. By leveraging large-scale FAERS data, multiple signal detection methodologies, and Weibull survival analysis, this research enhances the pharmacovigilance landscape, offering crucial insights for clinicians and regulatory authorities.