Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis

Miho Takemura; Kenji Ikemura; Masayoshi Kondo; Fumihiro Yamane; Mikiko Ueda; Masahiro Okuda

doi:10.1186/s40780-022-00252-z

Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis

J Pharm Health Care Sci. 2022 Aug 1;8(1):21. doi: 10.1186/s40780-022-00252-z.

Authors

Miho Takemura¹, Kenji Ikemura^{2

3}, Masayoshi Kondo⁴, Fumihiro Yamane⁴, Mikiko Ueda¹, Masahiro Okuda^{5

4}

Affiliations

¹ Department of Clinical Pharmacy Research and Education, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
² Department of Pharmacy, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan. ikemurak@hp-drug.med.osaka-u.ac.jp.
³ Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. ikemurak@hp-drug.med.osaka-u.ac.jp.
⁴ Department of Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
⁵ Department of Pharmacy, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Abstract

Background: Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HT₃RAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HT₃RA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HT₃RAs 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.

Methods: We retrospectively analyzed the effect of 5-HT₃RAs 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-HT₃RAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database.

Results: 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-HT₃RA) (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).

Conclusions: The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HT₃RAs in patients with the triple antiemetic therapy.

Keywords: 5-hydroxytryptamine type 3 receptor antagonist; Chemotherapy-induced nausea and vomiting; Cisplatin; Nephrotoxicity; Palonosetron.

Abstract

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