Takemura Miho, Ikemura Kenji, Kondo Masayoshi, Yamane Fumihiro, Ueda Mikiko, Okuda Masahiro
Department of Clinical Pharmacy Research and Education, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Pharmacy, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Pharm Health Care Sci. 2022 Aug 1;8(1):21. doi: 10.1186/s40780-022-00252-z.
Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HTRA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HTRAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis.
We retrospectively analyzed the effect of 5-HTRAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HTRAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database.
In a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HTRA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169-0.472).
The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HTRAs in patients with the triple antiemetic therapy.
顺铂（CDDP）诱导的肾毒性是CDDP治疗最重要的并发症。5-羟色胺3型受体拮抗剂（5-HTRAs）被广泛用于预防化疗引起的恶心和呕吐（CINV）。然而，在接受三联抗呕吐疗法（神经激肽-1受体拮抗剂、5-HTRA和地塞米松）的患者中，帕洛诺司琼与其他5-HTRAs相比，在CDDP诱导的肾毒性和CINV方面的优势尚不清楚。在本研究中，我们通过回顾性队列研究和药物警戒分析，研究了帕洛诺司琼对接受三联抗呕吐疗法患者中CDDP诱导的肾毒性和CINV的影响。
我们回顾性分析了110例接受CDDP、氟尿嘧啶和三联抗呕吐疗法治疗食管癌患者中5-HTRAs对肾毒性和CINV发生的影响。此外，使用日本药品不良反应报告（JADER）数据库，在接受三联抗呕吐疗法的患者中验证了5-HTRAs对CDDP诱导的肾毒性的影响。
在一项回顾性研究中，接受帕洛诺司琼治疗的患者中肾毒性（≥1级）的发生率（18%）显著低于接受雷莫司琼（另一种5-HTRA）治疗的患者（36%，p = 0.044）。此外，在一名接受雷莫司琼治疗的患者中观察到≥3级的严重肾毒性，而两组之间的血液学毒性相当（p = 0.553）。此外，接受帕洛诺司琼治疗的患者在CDDP给药后120小时内CINV的发生率（18%）显著低于接受雷莫司琼治疗的患者（39%，p = 0.026）。JADER数据库分析显示，帕洛诺司琼导致CDDP诱导的急性肾损伤的报告比值比为0.282（95%置信区间：0.169 - 0.472）。
本研究结果表明，在接受三联抗呕吐疗法的患者中，与其他5-HTRAs相比，帕洛诺司琼对CDDP诱导的肾毒性和CINV具有更大的潜在作用。
