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Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients

Abstract

We evaluated the effect of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) on the efficacy and safety of dasatinib for chronic-phase chronic myeloid leukemia (CP-CML). Retrospective analyses were performed for patients with CP-CML who received dasatinib at seven hospitals between April 2009 and December 2016. Seventy-three patients were identified, 16 of whom received PPIs or H2RAs concurrently with dasatinib. Major molecular response at 12 months was observed in 13 of 13 patients (100%) with concurrent PPIs or H2RAs (combination group), and in 23 of 51 patients (45.1%) who received only dasatinib (dasatinib-alone group; P < 0.001). Deep molecular response at 12 months was observed in four of six patients (66.7%) in the combination group, and seven of 38 patients (18.4%) in the dasatinib-alone group (P = 0.027). Dasatinib chemotherapy was stopped after 18 months for 25 patients (43.9%) from the dasatinib-alone group, but for none from the combination group. Combination treatment with PPIs or H2RAs did not reduce the efficacy of dasatinib. PPIs and H2RAs reduce the incidence of dasatinib discontinuation due to adverse events and increase the efficacy of dasatinib chemotherapy for patients.

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Acknowledgements

This work was supported by the Pharmacists Society of National Hospital Organization Kyushu. We would like to thank Dr. Michihiro Hidaka (National Hospital Organization [NHO] Kumamoto Medical Center) for his valuable comments and guidance. This study included the following seven medical institutions: NHO Kyushu Medical Center (Fukuoka, Fukuoka), NHO Kumamoto Medical Center (Kumamoto, Kumamoto), NHO Nagasaki Medical Center (Omura, Nagasaki), NHO Kagoshima Medical Center (Kagoshima, Kagoshima), NHO Kyushu Cancer Center (Fukuoka, Fukuoka), NHO Kokura Medical Center (Kitakyushu, Fukuoka), and NHO Fukuoka Higashi Medical Center (Koga, Fukuoka).

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Correspondence to Yoshimichi Koutake.

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All use of patient data was in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Koutake, Y., Taniguchi, J., Yasumori, N. et al. Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients. Int J Hematol 111, 826–832 (2020). https://doi.org/10.1007/s12185-020-02845-6

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  • DOI: https://doi.org/10.1007/s12185-020-02845-6

Keywords

  • Dasatinib
  • Proton pump inhibitors
  • H2-receptor antagonists
  • Chronic myeloid leukemia
  • Drug–drug interactions