Skip to main content

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

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.

Background

Cisplatin (CDDP) is a platinum-based drug that is widely used as first-line chemotherapy for various solid tumors, including lung, ovarian, bladder, testicular, head and neck, esophageal, gastric, and pancreatic cancers [1]. However, the use of CDDP is limited by occurrence of severe side effects in normal tissues, particularly nephrotoxicity. CDDP-induced nephrotoxicity occurs in approximately one-third of the patients receiving CDDP treatment, despite intensive prophylactic measures [2]. Therefore, co-administration of medicines with renal protective effects is crucial for the prevention of severe and irreversible damage to the kidney, and for the success of CDDP chemotherapy.

CDDP treatment has been classified as highly emetogenic chemotherapy [3]. The guidelines for antiemetic treatment recommend the use of triple antiemetic drugs (neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist (5-HT3RA), and dexamethasone) for cancer patients receiving highly emetogenic chemotherapy, including CDDP regimen [4,5,6]. The current guidelines recommend palonosetron as the preferred 5-HT3RA for preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving both moderately and highly emetogenic chemotherapeutic regimens [4,5,6]. A previous retrospective study reported that palonosetron suppressed CDDP-induced increases in serum creatinine (Scr) and blood urea nitrogen (BUN) levels from clinical data treated with CDDP and 5-HT3RAs [7]. Furthermore, an analysis using the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that first-generation 5-HT3RAs (ondansetron, granisetron, or ramosetron) significantly increased renal adverse events associated with CDDP as compared with a second-generation 5-HT3RA, palonosetron [8]. However, the advantage of palonosetron on CDDP-induced nephrotoxicity and CINV in comparison with other 5-HT3RAs remains unclear in patients with the triple antiemetic therapy.

In the present study, we retrospectively evaluated the effect of palonosetron on the development of nephrotoxicity and CINV in patients receiving CDDP, fluorouracil (5-FU), and triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis using the Japanese Adverse Drug Event Report (JADER) database.

Methods

Patients selection

Data of 122 patients hospitalized in Osaka University Hospital between January 2010 and December 2020, who received CDDP, 5-FU, and triple antiemetic therapy for the first time for the treatment of esophageal cancer and received triple antiemetic therapy, were extracted from the electronic medical records. Eligible patients received a continuous infusion of 5-FU (800 mg/m2) for 5 days, a 2-h intravenous infusion of CDDP (80 mg/m2), an oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), an intravenous infusion of dexamethasone (6.6 mg on day 1 through 4), and an intravenous infusion of ramosetron (0.3 mg on day 1 through 4) or palonosetron (0.75 mg on day 1). Patients were excluded if they had missing data, baseline Scr > 1.3 mg/dL, BUN > 22 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 100 IU/L, and hematological parameters grade ≥ 2 before chemotherapy, including white blood cell (WBC) count, platelet (PLT) count, absolute neutrophil count (ANC), or hemoglobin (Hb) level, defined as the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Evaluation of side effects following chemotherapy

We investigated the effect of 5-HT3RAs on the maximum values of Scr and BUN within 14 days following CDDP administration, the duration when CDDP-induced nephrotoxicity is usually observed [2]. In addition, the severity of nephrotoxicity within 14 days following CDDP administration was evaluated in accordance with the criteria for acute kidney injury defined as the CTCAE version 4.0 [9]. Hematological toxicity that developed within 28 days after CDDP administration was defined as grade ≥ 3 for WBC, PLT, ANC, or Hb. The incidence rates of CINV during the acute (0–24 h), delayed (24–120 h), and overall phase (0–120 h) following CDDP administration were investigated. Diabetes mellitus was defined by continued treatment with hypoglycemic drugs and fasting plasma glucose ≥126 mg/dL. Cardiovascular disease was defined as angina or myocardial infarction. Urinary and infusion volumes were calculated as the cumulative amount for 3 and 5 days following CDDP administration, respectively. The primary endpoint was the incidence of grade ≥ 1 nephrotoxicity. The secondary endpoints included the severity of nephrotoxicity, CINV, and hematological toxicity following CDDP administration.

Analyses on the effect of 5-HT3RAs on CDDP-associated acute kidney injury using the JADER database

Data on patient demographic information (DEMO), drug information (DRUG), adverse events (REAC), and primary disease (HIST) from April 2004 to September 2021 were obtained from the JADER database released by the PMDA (https://www.pmda.go.jp/). Data associated with CDDP and triple antiemetic therapy were extracted. Disease names were defined using the Medical Dictionary for Regulatory Activities (MedDRA/J) version 24.0. According to a previous report [10], the following six preferred term was used for searching CDDP-associated acute kidney injury: “acute kidney injury,” “renal impairment,” “renal failure,” “renal disorder,” “renal function test abnormal,” and “renal tubular disorder.” Effect of 5-HT3RAs on CDDP-associated acute kidney injury was evaluated using the reporting odds ratio (ROR). To calculate the ROR, CDDP-associated acute kidney injury and all other reported adverse events associated with CDDP were defined as “cases” and “non-cases,” respectively. The RORs were calculated from two-by-two contingency tables of counts with or without 5-HT3RA. RORs were expressed as point estimates with 95% confidence interval (CI).

Statistical analyses

Statistical comparisons between two groups were performed using the Mann-Whitney U test and Fisher’s exact test for continuous and categorical variables, respectively. Statistical analyses were performed using the GraphPad Prism version 8.4.3 (GraphPad Software Inc., San Diego, CA). A two-tailed p-value < 0.05 was considered statistically significant, and the confidence level was set to 95%.

Results

Patients’ characteristics

After considering inclusion and exclusion criteria, 110 of 122 patients were enrolled in the present study. Patient characteristics are summarized in Table 1. Forty-four patients (40%) received ramosetron, and 66 patients (60%) received palonosetron as 5-HT3RA. There were no significant differences in characteristics of patients treated with ramosetron and palonosetron.

Table 1 Patients’ characteristics

Nephrotoxicity, hematological toxicity, and CINV following administration of CDDP and 5-FU administration in patients receiving ramosetron and palonosetron

The number of patients with nephrotoxicity and hematological toxicity after CDDP and 5-FU administration in patients receiving ramosetron and palonosetron are shown in Table 2. The incidence of nephrotoxicity in patients receiving palonosetron (18%) was significantly lower than that in patients treated with ramosetron (36%, p = 0.044). Furthermore, grade ≥ 3 nephrotoxicity was observed in one patient treated with ramosetron. In contrast, there was no significant difference in the incidence of hematological toxicity between patients treated with ramosetron and palonosetron (p = 0.553).

Table 2 Number of patients with nephrotoxicity and hematological toxicity following CDDP and 5-FU administration

Figure 1 shows the comparison of the fold changes in Scr and BUN following CDDP and 5-FU administration between patients receiving ramosetron and palonosetron. As shown in Fig. 1, the fold change of Scr and BUN in patients receiving palonosetron was significantly lower than that in patients treated with ramosetron (p = 0.019 and 0.022, respectively).

Fig. 1
figure 1

Comparison of the fold changes of (A) Scr and (B) BUN following CDDP, 5-FU, and triple antiemetic therapy in patients treated with ramosetron (n = 44) and palonosetron (n = 66)

Figure 2 shows the comparison of incidence rates of CINV following CDDP administration between patients receiving ramosetron and palonosetron. During overall phase, the incidence rate of CINV in patients receiving palonosetron (18%) was significantly lower than in those receiving ramosetron (39%, p = 0.026). During the acute phase, nausea was observed in one patient (2%) each from ramosetron and palonosetron treatment groups. However, during the delayed phase, 16 patients (36%) treated with ramosetron and 11 patients (17%) with palonosetron developed nausea, with significantly low incidence rate of nausea in patients treated with palonosetron (p = 0.024). Furthermore, one patient (2%) each from ramosetron and palonosetron treatment groups had vomiting, however, severe vomiting of grade 2 was observed only in the patient treated with ramosetron.

Fig. 2
figure 2

Comparison of incidence rates of chemotherapy-induced nausea and vomiting (CINV) following CDDP, 5-FU, and triple antiemetic therapy in patients treated with ramosetron (n = 44) and palonosetron (n = 66)

Analyses on the effect of 5-HT3RAs on CDDP-associated acute kidney injury in patients received with CDDP and triple antiemetic therapy using the JADER database

The 751,497 reports in the JADER database from April 2004 to September 2021 were analyzed. A total of 288 cases of CDDP-associated acute kidney injury were identified among a total of 635 cases received with CDDP and triple antiemetic therapy. The results of reporting ratio of CDDP-associated acute kidney injury and RORs with 95% CI in patients receiving CDDP and triple antiemetic therapy are summarized in Table 3. JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% CI: 0.169–0.472), whereas there was absence of any significant signal for other 5-HT3RAs.

Table 3 Analyses on the effect of 5-HT3RAs on CDDP-associated acute kidney failure in patients received with CDDP and triple antiemetic therapy using the JADER database

Discussion

We identified the effect of palonosetron on CDDP-induced nephrotoxicity compared with that of other 5-HT3RAs in the present retrospective clinical study and pharmacovigilance analysis. To the best of our knowledge, this is the first study to report the effect of palonosetron on CDDP-induced nephrotoxicity in patients receiving CDDP, 5-FU, and triple antiemetic therapy.

In the present study, the fold change in Scr and BUN following CDDP administration in patients treated with palonosetron was significantly lower than that in patients treated with ramosetron (Fig. 1). In addition, the incidence of nephrotoxicity (grade ≥ 1) in patients receiving palonosetron was significantly lower than that in patients treated with ramosetron (Table 2), and grade ≥ 3 nephrotoxicity was observed in one patient treated with ramosetron. Moreover, the effect of palonosetron on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the JADER database. We could not get similar results in comparison between palonosetron and ramosetron because there were not enough cases of ramosetron use in JADER database to fully evaluate the effect of ramosetron (Table 3). These results are suggestive of better potential of palonosetron than ramosetron against CDDP-induced nephrotoxicity in patients with triple antiemetic therapy.

CDDP is excreted by the kidneys, and specifically accumulates in the renal proximal tubules [11]. CDDP is mainly transported to renal tissues via organic cation transporter 2 (OCT2) at the renal basolateral membrane [12, 13], whereas CDDP is excreted into urine through multidrug and toxin extrusion protein transporter 1 (MATE1), which is localized on the apical membrane [14], indicating that OCT2 and MATE1 should be responsible for CDDP-induced nephrotoxicity. As shown in a previous study using the mice model of CDDP-induced nephrotoxicity [8], the concomitant use of a first-generation 5-HT3RA (ondansetron, granisetron, or ramosetron) significantly increased CDDP accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of CDDP alone. An uptake study in hMATE1-expressing HEK293 cells revealed that the first-generation 5-HT3RAs have a lower IC50 than palonosetron, thus, palonosetron is thought to have weaker MATE1 inhibitory activity than the first-generation 5-HT3RAs [8]. Furthermore, palonosetron was reported to interfere with OCT2 activity [15]. Taking these findings into consideration, we speculate that palonosetron ameliorated CDDP-induced nephrotoxicity by decreasing the accumulation of CDDP in the kidney via OCT2. However, further studies are needed to elucidate the detailed mechanism of protective effect of palonosetron against CDDP-induced nephrotoxicity.

Nevertheless, inhibition of OCT2-mediated transport of CDDP by 5-HT3RAs is expected to increase its plasma concentration, which may lead to hematological side effects associated with CDDP. In the present study, there was no significant difference in the incidence of hematological toxicity between patients treated with palonosetron and ramosetron (Table 2). However, a previous study reported that combination treatment with palonosetron did not affect the blood levels of CDDP in mice [8]. Thus, it is likely that plasma concentration of CDDP is not affected by co-administration of palonosetron and/or ramosetron.

CINV results in significant morbidity, adversely affects patient’s quality of life, and leads to poor compliance with treatment regimens [16,17,18]. The present study showed that the incidence rates of CINV in patients treated with palonosetron were significantly lower than in those receiving ramosetron during both delayed phase and overall phase (Fig. 2). Palonosetron has a longer half-life in plasma and a higher binding affinity than first-generation 5-HT3RAs [19]. A previous study reported that palonosetron was significantly more effective than tropisetron (a first-generation 5-HT3RA) in controlling delayed emesis in patients receiving high dose of CDDP [20]. Moreover, palonosetron has been reported to be cost-effective treatment strategy for the prophylaxis of CINV in highly and moderately emetogenic chemotherapy compared to other 5-HT3RAs [21, 22]. Therefore, these findings suggested palonosetron as a potential alternative for controlling CINV in patients receiving highly emetogenic chemotherapy, including CDDP regimen.

This study had several limitations. First, it remains unclear whether palonosetron directly inhibits OCT2-mediated renal uptake of CDDP. Second, the plasma concentration of CDDP was not assessed in the present study. Finally, the level of evidence was poor because this was a retrospective study that included a small number of patients from a single institution. Thus, additional in vitro and in vivo studies with large and diverse samples are warranted to validate our findings and to reveal altered pharmacokinetics of CDDP by co-administration of palonosetron.

Conclusions

In conclusion, our study is the first to demonstrate that palonosetron is more effective in preventing CDDP-induced nephrotoxicity and CINV than other 5-HT3RAs. The present findings provide important information to optimize the current treatment regimens to minimize CDDP-induced nephrotoxicity.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

5-FU:

fluorouracil

5-HT3RA:

5-hydroxytryptamine type 3 receptor antagonist

ALT:

alanine aminotransferase

ANC:

absolute neutrophil count

AST:

aspartate aminotransferase

BUN:

blood urea nitrogen

CDDP:

cisplatin

CI:

confidence interval

CINV:

chemotherapy-induced nausea and vomiting

CTCAE:

Common Terminology Criteria for Adverse Events

Hb:

hemoglobin

JADER:

Japanese Adverse Drug Event Report

MATE1:

multidrug and toxin extrusion protein transporter 1

MedDRA:

Medical Dictionary for Regulatory Activities

NSAIDs:

non-steroidal anti-inflammatory drugs

OCT2:

organic cation transporter 2

PLT:

platelet

PPI:

proton pump inhibitor

ROR:

reporting odds ratio

Scr:

serum creatinine

WBC:

white blood cell

References

  1. Boulikas T, Vougiouka M. Recent clinical trials using cisplatin, carboplatin and their combination chemotherapy drugs (review). Oncol Rep. 2004;11:559–95.

    CAS  PubMed  Google Scholar 

  2. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73:994–1007.

    CAS  Article  Google Scholar 

  3. Wilder-Smith OH, Borgeat A, Chappuis P, Fathi M, Forni M. Urinary serotonin metabolite excretion during cisplatin chemotherapy. Cancer. 1993;72:2239–41.

    CAS  Article  Google Scholar 

  4. Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38:2782–97.

    CAS  Article  Google Scholar 

  5. Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27:v119–33.

    CAS  Article  Google Scholar 

  6. Takeuchi H, Saeki T, Aiba K, Tamura K, Aogi K, Eguchi K, et al. Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary. Int J Clin Oncol. 2016;21:1–12.

    Article  Google Scholar 

  7. Wakai E, Suzumura Y, Ikemura K, Mizuno T, Watanabe M, Takeuchi K, et al. An integrated in silico and in vivo approach to identify protective effects of palonosetron in cisplatin-induced nephrotoxicity. Pharmaceuticals (Basel). 2020;13:480.

    CAS  Article  Google Scholar 

  8. Goda M, Kanda M, Yoshioka T, Yoshida A, Murai Y, Zamami Y, et al. Effects of 5-HT3 receptor antagonists on cisplatin-induced kidney injury. Clin Transl Sci. 2021;14:1906–16.

    CAS  Article  Google Scholar 

  9. Ikemura K, Oshima K, Enokiya T, Okamoto A, Oda H, Mizuno T, et al. Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study. Cancer Chemother Pharmacol. 2017;79:943–9.

    CAS  Article  Google Scholar 

  10. Naganuma M, Motooka Y, Sasaoka S, Hatahira H, Hasegawa S, Fukuda A, et al. Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese adverse drug event report database. SAGE Open Med. 2018;6:2050312118772475.

    Article  Google Scholar 

  11. Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther. 1980;213:551–6.

    CAS  PubMed  Google Scholar 

  12. Filipski KK, Loos WJ, Verweij J, Sparreboom A. Interaction of cisplatin with the human organic cation transporter 2. Clin Cancer Res. 2008;14:3875–80.

    CAS  Article  Google Scholar 

  13. Ciarimboli G, Ludwig T, Lang D, Pavenstädt H, Koepsell H, Piechota HJ, et al. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005;167:1477–84.

    CAS  Article  Google Scholar 

  14. Yonezawa A, Inui K. Organic cation transporter OCT/SLC22A and H(+)/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents. Biochem Pharmacol. 2011;81:563–8.

    CAS  Article  Google Scholar 

  15. George B, Wen X, Jaimes EA, Joy MS, Aleksunes LM. In vitro inhibition of renal OCT2 and MATE1 secretion by antiemetic drugs. Int J Mol Sci. 2021;22:6439.

    CAS  Article  Google Scholar 

  16. Ballatori E, Roila F, Ruggeri B, Betti M, Sarti S, Soru G. The impact of chemotherapy-induced nausea and vomiting on health-related quality of life. Support Care Cancer. 2007;15:179–85.

    Article  Google Scholar 

  17. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006;24:4472–8.

    CAS  Article  Google Scholar 

  18. Cohen L, de Moor CA, Eisenberg P, Ming EE, Hu H. Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer. 2007;15:497–503.

    Article  Google Scholar 

  19. Navari RM. Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Future Oncol. 2006;2:591–602.

    CAS  Article  Google Scholar 

  20. Li RC, Zheng LJ, Qiu H. Comparison of the effect of palonosetron versus tropisetron in prevention of vomiting in patients receiving high dose cisplatin-based chemotherapy. Zhonghua Zhong Liu Za Zhi. 2012;34:228–31.

    CAS  PubMed  Google Scholar 

  21. Giuliani J, Bonetti A. Netupitant plus palonosetron is a cost-effective treatment for the prophylaxis of chemotherapy-induced nausea and vomiting in highly and moderately emetogenic cancer treatment. Expert Rev Pharmacoecon Outcomes Res. 2019;19:505–8.

    Article  Google Scholar 

  22. Giuliani J, Bonetti A. Cost-effectiveness of newer regimens for the prophylaxis of chemotherapy-induced nausea and vomiting: review of the literature and real-world data. Curr Opin Oncol. 2020;32:269–73.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Editage (www.editage.jp) for English language editing.

Funding

This work was supported by a Grant-in-Aid for Scientific Research (C) [20 K07131 and 21 K06689] from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Contributions

MT, KI, and MO contributed to the study conception and design. MT and KI performed material preparation, data collection, and analysis. MK and FY were involved in JADER database analyses. KI, MU, and MO critically revised the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Kenji Ikemura.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethical review board of Osaka University Hospital (No. 16002–10). Informed consent was obtained via opt-out through the website.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Takemura, M., Ikemura, K., Kondo, M. et al. Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis. J Pharm Health Care Sci 8, 21 (2022). https://doi.org/10.1186/s40780-022-00252-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40780-022-00252-z

Keywords

  • Cisplatin
  • Nephrotoxicity
  • Chemotherapy-induced nausea and vomiting
  • 5-hydroxytryptamine type 3 receptor antagonist
  • Palonosetron