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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

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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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References

  1. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330–40.

    Article  CAS  Google Scholar 

  2. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.

    Article  CAS  Google Scholar 

  3. O’Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005;65:4500–5.

    Article  Google Scholar 

  4. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, et al. Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004;47:6658–61.

    Article  CAS  Google Scholar 

  5. Das J, Chen P, Norris D, Padmanabha R, Lin J, Moquin RV, et al. 2-Aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. J Med Chem. 2006;49:6819–32.

    Article  CAS  Google Scholar 

  6. Shayani S. Dasatinib, a multikinase inhibitor: therapy, safety, and appropriate management of adverse events. Ther Drug Monit. 2010;32:680–7.

    Article  CAS  Google Scholar 

  7. Eley T, Luo FR, Agrawal S, Sanil A, Manning J, Li T, et al. Phase I study of the effect of gastric acid pH modulators on the bioavailability of oral dasatinib in healthy subjects. J Clin Pharmacol. 2009;49:700–9.

    Article  CAS  Google Scholar 

  8. Yagasaki F, Niwa T, Abe A, Ishikawa M, Kato C, Ogura K, et al. Correlation of quantification of major bcr-abl mRNA between TMA (transcription mediated amplification) method and real-time quantitative PCR. Rinsho Ketsueki. 2009;50:481–7.

    PubMed  Google Scholar 

  9. Abe A, Minami Y, Hayakawa F, Kitamura K, Nomura Y, Murata M, et al. Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy. Int J Hematol. 2008;88:471–5.

    Article  CAS  Google Scholar 

  10. Nakamae H, Yoshida C, Miyata Y, Hidaka M, Uike N, Koga D, et al. A new diagnostic kit, ODK-1201, for the quantitation of low major BCR-ABL mRNA level in chronic myeloid leukemia: correlation of quantitation with major BCR-ABL mRNA kits. Int J Hematol. 2015;102:304–11.

    Article  CAS  Google Scholar 

  11. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  12. Takahashi N, Miura M, Niioka T, Sawada K. Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib pharmacokinetics in Japanese leukemia patients. Cancer Chemother Pharmacol. 2012;69:999–1004.

    Article  CAS  Google Scholar 

  13. Pape E, Michel D, Scala-Bertola J, Schiestel T, Harlé A, Bouchet S, et al. Effect of esomeprazole on the oral absorption of dasatinib in a patient with Philadelphia-positive acute lymphoblastic leukemia. Br J Clin Pharmacol. 2016;81:1195–6.

    Article  Google Scholar 

  14. Kletzl H, Giraudon M, Ducray PS, Abt M, Hamilton M, Lum BL. Effect of gastric pH on erlotinib pharmacokinetics in healthy individuals: omeprazole and ranitidine. Anticancer Drugs. 2015;26:565–72.

    Article  CAS  Google Scholar 

  15. Yin OQ, Gallagher N, Fischer D, Demirhan E, Zhou W, Golor G, et al. Effect of the proton pump inhibitor esomeprazole on the oral absorption and pharmacokinetics of nilotinib. J Clin Pharmacol. 2010;50:960–7.

    Article  CAS  Google Scholar 

  16. Lam LH, Capparelli EV, Kurzrock R. Association of concurrent acid-suppression therapy with survival outcomes and adverse event incidence in oncology patients receiving erlotinib. Cancer Chemother Pharmacol. 2016;78:427–32.

    Article  CAS  Google Scholar 

  17. Yin OQ, Giles FJ, Baccarani M, le Coutre P, Chiparus O, Gallagher N, et al. Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia. Cancer Chemother Pharmacol. 2012;70:345–50.

    Article  CAS  Google Scholar 

  18. Wang X, Roy A, Hochhaus A, Kantarjian HM, Chen TT, Shah NP. Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure-response analysis of a Phase III study. Clin Pharmacol. 2013;5:85–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, et al. Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia. Eur J Clin Pharmacol. 2016;72:185–93.

    Article  CAS  Google Scholar 

  20. Osorio S, Escudero-Vilaplana V, Gómez-Centurión I, Pérez-López R, Ayala R, Vall-Llovera F, et al. Drug-to-drug interactions of tyrosine kinase inhibitors in chronic myeloid leukemia patients. Is it a real problem? Ann Hematol. 2018;97:2089–98.

    Article  CAS  Google Scholar 

  21. Nagata Y, Ohashi K, Fukuda S, Kamata N, Akiyama H, Sakamaki H. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol. 2010;91:799–807.

    Article  Google Scholar 

  22. Tanaka H, Nakashima S, Usuda M. Rapid and sustained increase of large granular lymphocytes and rare cytomegalovirus reactivation during dasatinib treatment in chronic myelogenous leukemia patients. Int J Hematol. 2012;96:308–19.

    Article  CAS  Google Scholar 

  23. Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer. 2010;116:377–86.

    Article  CAS  Google Scholar 

  24. Chuah CT, Nakamae H, Shen ZX, Bradley-Garelik MB, Kim DW. Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma. 2014;55:2093–100.

    Article  CAS  Google Scholar 

  25. Nakamae H, Fujisawa S, Ogura M, Uchida T, Onishi Y, Taniwaki M, et al. Dasatinib versus imatinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia: a subanalysis of the DASISION 5-year final report. Int J Hematol. 2017;105:792–804.

    Article  CAS  Google Scholar 

  26. Hagihara M, Iriyama N, Yoshida C, Wakita H, Chiba S, Okamoto S, et al. Association of pleural effusion with an early molecular response in patients with newly diagnosed chronic-phase chronic myeloid leukemia receiving dasatinib: results of a D-First study. Oncol Rep. 2016;36:2976–82.

    Article  CAS  Google Scholar 

  27. Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? Crit Rev Oncol Hematol. 2014;89:242–7.

    Article  Google Scholar 

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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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