Nephrotoxicity Evaluation on Cisplatin Combined with 5-HT(3) Receptor Antagonists: A Retrospective Study

OBJECTIVE: 5-HT(3) receptor antagonist (ondansetron) has been reported to have nephrotoxic effect when combined with cisplatin in mice; however, little evidence exists in explaining its nephrotoxic effects on patients. The aim of this present study was to investigate whether 5-HT(3) receptor antagonist could enhance or aggravate the incidence of cisplatin-induced nephrotoxicity in patients. METHODS: We retrospectively reviewed 600 tumor patients which were treated with cisplatin (⩾60 mg/m(2)) as a first-time chemotherapy and combined with 5-HT(3) receptor antagonist (i.e., ondansetron, tropisetron, or ramosetron, each kind of 5-HT(3) receptor antagonist contains 200 cases) between January 2010 and December 2015. Cisplatin dosing, the baseline creatinine clearance, and other independent risk factors such as patient's age, sex, PS score, and weight associated with nephrotoxicity were evaluated in a multivariable model. RESULTS: The incidence of Grade ⩾ 2 serum creatinine elevation in cisplatin + ondansetron group was significantly higher than cisplatin + tropisetron group (P = 0.04), but no significant difference was found between cisplatin + ondansetron group and cisplatin + ramosetron group (P = 0.3). It was also found that cisplatin dosage and tumor type were independent risk factors in the development of nephrotoxicity. CONCLUSION: Higher cisplatin dosage and regular use of ondansetron combined with cisplatin are more likely to increase the incidence of nephrotoxicity; tropisetron showed the relatively mild effect on kidney function, suggesting that tropisetron is a preferable alternative in the process of cisplatin chemotherapy.