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Supportive Care in Cancer

, Volume 27, Issue 3, pp 849–856 | Cite as

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

  • Hirofumi Hamano
  • Marin Mitsui
  • Yoshito ZamamiEmail author
  • Kenshi Takechi
  • Takahiro Nimura
  • Naoto Okada
  • Keijo Fukushima
  • Masaki Imanishi
  • Masayuki Chuma
  • Yuya Horinouchi
  • Yuki Izawa-Ishizawa
  • Yasushi Kirino
  • Toshimi Nakamura
  • Kazuhiko Teraoka
  • Yasumasa Ikeda
  • Hiromichi Fujino
  • Hiroaki Yanagawa
  • Toshiaki Tamaki
  • Keisuke Ishizawa
Original Article

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.

Keywords

Irinotecan SN-38 Alkalization drugs JADER Supportive care 

Notes

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 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.

Compliance with ethical standards

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.

Supplementary material

520_2018_4367_MOESM1_ESM.docx (32 kb)
ESM 1 (DOCX 31 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hirofumi Hamano
    • 1
    • 2
  • Marin Mitsui
    • 2
  • Yoshito Zamami
    • 1
    • 2
    Email author
  • Kenshi Takechi
    • 3
  • Takahiro Nimura
    • 2
  • Naoto Okada
    • 1
  • Keijo Fukushima
    • 4
  • Masaki Imanishi
    • 1
  • Masayuki Chuma
    • 3
  • Yuya Horinouchi
    • 5
  • Yuki Izawa-Ishizawa
    • 5
  • Yasushi Kirino
    • 1
  • Toshimi Nakamura
    • 1
  • Kazuhiko Teraoka
    • 1
  • Yasumasa Ikeda
    • 5
  • Hiromichi Fujino
    • 4
  • Hiroaki Yanagawa
    • 3
  • Toshiaki Tamaki
    • 5
  • Keisuke Ishizawa
    • 1
    • 2
  1. 1.Department of PharmacyTokushima University HospitalTokushimaJapan
  2. 2.Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  3. 3.Clinical Trial Center for Developmental TherapeuticsTokushima University HospitalTokushimaJapan
  4. 4.Department of Molecular Pharmacology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  5. 5.Department of Pharmacology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan

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