The First Hospital of Lanzhou University, Pharmacy Department, Lanzhou, China.
The First Hospital of Lanzhou University, Third Department of General Surgery, Lanzhou, China.
Biomed Res Int. 2018 May 30;2018:1024324. doi: 10.1155/2018/1024324. eCollection 2018.
5-HT 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 receptor antagonist could enhance or aggravate the incidence of cisplatin-induced nephrotoxicity in patients.
We retrospectively reviewed 600 tumor patients which were treated with cisplatin (60 mg/m) as a first-time chemotherapy and combined with 5-HT receptor antagonist (i.e., ondansetron, tropisetron, or ramosetron, each kind of 5-HT 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.
The incidence of Grade 2 serum creatinine elevation in cisplatin + ondansetron group was significantly higher than cisplatin + tropisetron group ( = 0.04), but no significant difference was found between cisplatin + ondansetron group and cisplatin + ramosetron group ( = 0.3). It was also found that cisplatin dosage and tumor type were independent risk factors in the development of nephrotoxicity.
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.
已有报道称，5-羟色胺受体拮抗剂（昂丹司琼）与顺铂联合使用时，在小鼠体内具有肾毒性作用；然而，目前几乎没有证据可以解释其对患者的肾毒性作用。本研究旨在探讨 5-羟色胺受体拮抗剂是否会增强或加重顺铂引起的患者肾毒性的发生率。
我们回顾性分析了 2010 年 1 月至 2015 年 12 月期间接受顺铂（60mg/m2）作为首次化疗并联合 5-羟色胺受体拮抗剂（昂丹司琼、托烷司琼或雷莫司琼，每类 5-羟色胺受体拮抗剂各 200 例）治疗的 600 例肿瘤患者。在多变量模型中评估了顺铂剂量、基线肌酐清除率以及与肾毒性相关的其他独立危险因素，如患者年龄、性别、PS 评分和体重。
顺铂+昂丹司琼组血清肌酐升高 2 级的发生率明显高于顺铂+托烷司琼组（=0.04），但顺铂+昂丹司琼组与顺铂+雷莫司琼组之间无显著差异（=0.3）。此外，还发现顺铂剂量和肿瘤类型是肾毒性发生的独立危险因素。
较高的顺铂剂量和常规使用昂丹司琼联合顺铂更有可能增加肾毒性的发生率；托烷司琼对肾功能的影响相对较小，提示在顺铂化疗过程中托烷司琼是一种较好的选择。
