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Nephrotoxicity Evaluation on Cisplatin Combined with 5-HT3 Receptor Antagonists: A Retrospective Study
Wen Kou1, Hongyan Qin1, Shahbaz Hanif2
1The First Hospital of Lanzhou University, Pharmacy Department, Lanzhou, China.
Objective:
5-HT3 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-HT3 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/m2) as a first-time chemotherapy and combined with 5-HT3 receptor antagonist (i.e., ondansetron, tropisetron, or ramosetron, each kind of 5-HT3 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.
Insights
Ondansetron combined with cisplatin increases nephrotoxicity risk more than tropisetron. Tropisetron is a safer alternative for patients undergoing cisplatin chemotherapy, showing milder kidney function effects.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- 5-HT3 receptor antagonists, like ondansetron, may cause nephrotoxicity with cisplatin.
- Limited data exists on these effects in human patients.
- This study investigates the impact of 5-HT3 receptor antagonists on cisplatin-induced nephrotoxicity.
Purpose of the Study:
- To determine if 5-HT3 receptor antagonists enhance or aggravate cisplatin-induced nephrotoxicity in patients.
- To compare the nephrotoxic effects of ondansetron, tropisetron, and ramosetron when used with cisplatin.
Main Methods:
- Retrospective review of 600 tumor patients receiving cisplatin (≥60 mg/m²) chemotherapy.
- Analysis of patients treated with cisplatin combined with ondansetron, tropisetron, or ramosetron (200 cases each).
- Evaluation of cisplatin dosage, baseline creatinine clearance, and risk factors in a multivariable model.
Main Results:
- Higher incidence of Grade ≥2 serum creatinine elevation in the cisplatin + ondansetron group compared to cisplatin + tropisetron (P=0.04).
- No significant difference in nephrotoxicity between cisplatin + ondansetron and cisplatin + ramosetron groups (P=0.3).
- Cisplatin dosage and tumor type identified as independent risk factors for nephrotoxicity.
Conclusions:
- Higher cisplatin dosage and regular ondansetron use increase nephrotoxicity risk.
- Tropisetron demonstrates a milder effect on kidney function, making it a preferable alternative.
- Findings suggest careful selection of 5-HT3 receptor antagonists during cisplatin chemotherapy is crucial.
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