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Irinotecan-induced neutropenia is reduced by oral alkalization drugs: analysis using retrospective chart reviews and the spontaneous reporting database

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Abstract

Purpose

SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied. The aim of this study was to investigate the relationship between oral alkalization drugs and neutropenia in irinotecan-treated patients.

Methods and results

Patients with cervical or ovarian cancer were administered irinotecan and investigated by medical chart reviews to determine whether oral alkalization drugs were effective at ameliorating irinotecan-induced neutropenia. The drug combination in the oral alkalization drugs—ursodeoxycholic acid, magnesium oxide, and sodium hydrogen carbonate—significantly improved neutrophil counts and reduced dose intensity compared with those of non-users. In the large-scale Japanese Adverse Drug Event Report database, the reporting odds ratio of irinotecan-induced neutropenia was significantly lower when irinotecan had been given in combination with oral alkalization drugs.

Conclusions

These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely.

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Acknowledgements

We thank Dr. Kakei Ryu, A. I. E. Ltd. (Hana pharmacy), emem pharmacy, SANKO PHARMACY Co., ltd. and the other contributors for crowdfunding the present research launched by Otsucle Aim for development of preventive drug against side effects of anticancer agent (Tokushima, Japan).

Author information

Author notes

  1. Hirofumi Hamano and Marin Mitsui contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan

    Hirofumi Hamano, Yoshito Zamami, Naoto Okada, Masaki Imanishi, Yasushi Kirino, Toshimi Nakamura, Kazuhiko Teraoka & Keisuke Ishizawa

  2. Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Hirofumi Hamano, Marin Mitsui, Yoshito Zamami, Takahiro Nimura & Keisuke Ishizawa

  3. Clinical Trial Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan

    Kenshi Takechi, Masayuki Chuma & Hiroaki Yanagawa

  4. Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Keijo Fukushima & Hiromichi Fujino

  5. Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasumasa Ikeda & Toshiaki Tamaki

Authors
  1. Hirofumi Hamano
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  2. Marin Mitsui
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  3. Yoshito Zamami
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  19. Keisuke Ishizawa
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Contributions

Study conception and design: H.H. Performed the experiments and data acquisition: H.H., M.M. Analysis and interpretation of data: H.H., M.M., Y.Z., K.T., T.N, N.O., K.F., Y.I., Y.H., Y.I., M.I., K.T., T.N., Y.K., H.F., H.Y., T.T. and K.I. Drafting the work or critically revising it for important intellectual content: H.H., Y.Z.

Corresponding author

Correspondence to Yoshito Zamami.

Ethics declarations

This study and all protocols were reviewed and approved by the Ethics Committee of Tokushima University Hospital (approval number: 2059-4).

Conflict of interest

The authors declare that they have no conflict of interest.

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Hamano, H., Mitsui, M., Zamami, Y. et al. Irinotecan-induced neutropenia is reduced by oral alkalization drugs: analysis using retrospective chart reviews and the spontaneous reporting database. Support Care Cancer 27, 849–856 (2019). https://doi.org/10.1007/s00520-018-4367-y

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  • DOI: https://doi.org/10.1007/s00520-018-4367-y

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