Adverse events of capecitabine in gastric cancer patients: a real-world pharmacovigilance study based on the FAERS database.

BACKGROUND: Capecitabine stands as a pivotal chemotherapeutic agent in gastric cancer (GC) management. While its general safety profile has been documented, comparative pharmacovigilance analyses of distinct capecitabine-based treatment regimens among GC patients remain scarce. METHODS: This study extracted AE reports from the United States Food and Drug Administration AE Reporting System (FAERS) for the period 2004 Q1-2024 Q4. Following rigorous data cleansing, the adverse event (AE) reports were systematically standardized using the system organ class (SOC) and preferred term (PT) terminology from the Medical Dictionary for Regulatory Activities (MedDRA, version 26.0). Four disproportionality algorithms were employed to detect and analyze AE signals across four cohorts. Cohort 1 was from capecitabine monotherapy. Cohort 2 represented capecitabine in combination with other chemotherapeutic agents. Cohort 3 was for capecitabine in combination with other chemotherapeutic and targeted agents. Cohort 4 was from the capecitabine in combination with other chemotherapeutic agents as well as immunosuppressants. RESULTS: A total of 1,681 AE reports associated with capecitabine were included (632 cases in Cohort 1, 816 cases in Cohort 2, 189 cases in Cohort 3, and 44 cases in Cohort 4). The outcomes of AEs were predominantly other medical events, hospitalization or prolonged hospitalization, and death. Gastrointestinal disorders, general disorders and administration site conditions were the most frequently affected SOCs. The most frequent AEs in Cohort 1 were death (n = 83), diarrhea (n = 75), and nausea (n = 73), whereas the strongest signal was palmar-plantar erythrodysaesthesia syndrome (n = 43, ROR = 4.62). In Cohort 2, diarrhoea (n = 160), vomiting (n = 146), and nausea (n = 143) were the most frequently reported AEs, whereas palmar-plantar erythrodysaesthesia syndrome showed the strongest signal (n = 95, ROR = 6.69). In Cohort 3, leukoencephalopathy exhibited the strongest signal (n = 7, ROR = 21.79). In Cohort 4, sleep disorder (n = 5, ROR = 95.98, 95% CI: 33.54-274.69), dry mouth (n = 5, ROR = 35.98, 95% CI: 13.89-93.18), and inappropriate schedule of product administration (n = 5, ROR = 28.78, 95% CI: 11.25-73.59) appeared as novel, robust signals. CONCLUSION: Capecitabine showed distinct AE profiles in different GC regimens, with both prevalent and rare signals. Tailored safety monitoring is needed based on combination regimens.