Skip to main content
Top
Published in: International Journal of Hematology 6/2020

01-06-2020 | Chronic Myeloid Leukemia | Original Article

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

Authors: Yoshimichi Koutake, Jun Taniguchi, Naoko Yasumori, Hiroki Nagaishi, Tomoaki Eto, Kotaro Nakashima, Mami Fukazawa, Toshinobu Hayashi

Published in: International Journal of Hematology | Issue 6/2020

Login to get access

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.
Literature
1.
2.
go back to reference 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.CrossRef 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.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference Shayani S. Dasatinib, a multikinase inhibitor: therapy, safety, and appropriate management of adverse events. Ther Drug Monit. 2010;32:680–7.CrossRef Shayani S. Dasatinib, a multikinase inhibitor: therapy, safety, and appropriate management of adverse events. Ther Drug Monit. 2010;32:680–7.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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 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
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRef Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? Crit Rev Oncol Hematol. 2014;89:242–7.CrossRef Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? Crit Rev Oncol Hematol. 2014;89:242–7.CrossRef
Metadata
Title
Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients
Authors
Yoshimichi Koutake
Jun Taniguchi
Naoko Yasumori
Hiroki Nagaishi
Tomoaki Eto
Kotaro Nakashima
Mami Fukazawa
Toshinobu Hayashi
Publication date
01-06-2020
Publisher
Springer Singapore
Published in
International Journal of Hematology / Issue 6/2020
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-020-02845-6

Other articles of this Issue 6/2020

International Journal of Hematology 6/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine