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Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study

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Abstract

Purpose

The nephrotoxicity of cisplatin (CDDP) is its dose-limiting side effect, and is caused by renal accumulation of CDDP mainly via organic cation transporter 2 (OCT2). Because proton pump inhibitors (PPIs) are known to inhibit OCT2 activity, PPI might ameliorate CDDP-induced nephrotoxicity. In the present study, we retrospectively investigated the effect of co-administration of PPI on CDDP-induced nephrotoxicity.

Methods

We analyzed the impact of PPI on the development of nephrotoxicity in 133 patients who received CDDP and fluorouracil (5-FU) therapy for the treatment of esophageal cancer or head and neck cancer. Nephrotoxicity that developed within 14 days following CDDP administration was evaluated in accordance with Common Terminology Criteria for Adverse Events ver. 4.0 for acute kidney injury.

Results

The rate of nephrotoxicity in patients with PPI (12%, n = 33) was significantly lower than that in patients without PPI (30%, n = 100). Severe nephrotoxicity greater than Grade 2 was not observed in patients with PPI, whereas the rate of hematological toxicity was comparable between patients with and without PPI. Kaplan–Meier analysis showed that the time to nephrotoxicity following CDDP administration was significantly prolonged in patients with PPI. Multivariate analysis revealed that co-administration of PPI with CDDP and 5-FU was an independent factor significantly contributing to the amelioration of nephrotoxicity (odds ratio 0.239, p = 0.033).

Conclusions

These findings indicate that co-administration of clinical doses of PPI could ameliorate nephrotoxicity without exacerbation of hematological toxicity in patients receiving CDDP and 5-FU therapy.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (C) [Grant 26460195 and 26460196] from the Japan Society for the Promotion of Science. We would like to thank Editage (http://www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Pharmacy, Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Kenji Ikemura, Tomoyuki Enokiya, Akiharu Okamoto, Yuichi Muraki, Takuya Iwamoto & Masahiro Okuda

  2. Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan

    Kosuke Oshima

  3. Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan

    Hiroyasu Oda, Toshiro Mizuno & Naoyuki Katayama

  4. Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan

    Hajime Ishinaga & Kazuhiko Takeuchi

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  1. Kenji Ikemura
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  2. Kosuke Oshima
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Correspondence to Masahiro Okuda.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent was not required.

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Ikemura, K., Oshima, K., Enokiya, 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 79, 943–949 (2017). https://doi.org/10.1007/s00280-017-3296-7

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  • DOI: https://doi.org/10.1007/s00280-017-3296-7

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