Comparative effectiveness and safety of ondansetron-based dual versus triple antiemetic regimens for chemotherapy-induced nausea and vomiting.

Chemotherapy-induced nausea and vomiting remains a frequent complication of cytotoxic therapy and can compromise treatment tolerance and adherence. This retrospective propensity score-matched cohort study evaluated the comparative effectiveness and safety of ondansetron-based dual versus triple antiemetic regimens in patients receiving chemotherapy for malignant tumors. Consecutive patients treated between January 2022 and July 2023 who underwent at least 2 chemotherapy cycles were identified from hospital records. Patients received either a dual regimen (ondansetron plus dexamethasone or aprepitant) or a triple regimen (ondansetron plus dexamethasone plus aprepitant). Propensity score matching (1:1) was conducted using sex, age, tumor type, metastatic status, Karnofsky performance status score, and history of motion sickness to reduce confounding, yielding 319 matched pairs. Across the first 2 chemotherapy cycles, the triple regimen achieved higher control rates for nausea and vomiting than the dual regimen, with statistically significant differences in overall efficacy in both cycles. Subgroup analyses suggested the greatest benefit of triple therapy among patients receiving highly emetogenic chemotherapy, whereas both strategies achieved high efficacy in moderately emetogenic settings. Adverse reactions were more frequent with the triple regimen in the first cycle, while between-group differences were attenuated in the second cycle. These findings support a risk-adapted approach that prioritizes triple therapy for highly emetogenic regimens with attention to tolerability.