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

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

doi:10.1007/s12185-020-02845-6

Cited by 5 publications

(1 citation statement)

References 25 publications

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“…Several studies have investigated the DDIs between PPIs and TKIs; the results are contradictory concerning PPI interaction with the bioavailability and activity of TKIs. A summary of these DDIs is presented in Table 3 ( Rugo et al, 2005 ; Egorin et al, 2009 ; Yin et al, 2010 ; Yin et al, 2012 ; Takahashi et al, 2012 ; Hilton et al, 2013 ; Abbas et al, 2013 ; Musib et al, 2013 ; Tan et al, 2013 ; Johansson et al, 2014 ; Narasimhan et al, 2014 ; Chu et al, 2015 ; Kletzl et al, 2015 ; Ha et al, 2015 ; Iurlo et al, 2016 ; Kumarakulasinghe et al, 2016 ; Lam et al, 2016 ; Zenke et al, 2016 ; Chu et al, 2017 ; Lalani et al, 2017 ; Lacy et al, 2017 ; Lau et al, 2017 ; Morcos et al, 2017 ; Yokota et al, 2017 ; de Jong et al, 2018 ; Nieves Sedano et al, 2018 ; Ohgami et al, 2018 ; Fang et al, 2019 ; Mir et al, 2019 ; Vishwanathan et al, 2018 ; Pisano et al, 2019 ; de Man et al, 2019 ; Koutake et al, 2020 ; Ruanglertboon et al, 2020 ; Van De Sijpe et al, 2020 ; Chen et al, 2021 ; Rassy et al, 2021 ). Table 4 summarizes the main studies reporting reductions in the survival of patients receiving this combination of medication ( Chu et al, 2015 ; Ha et al, 2015 ; Fang et al, 2019 ; Mir et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Proton Pump Inhibitors and Cancer: Current State of Play

2022

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Background: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are overprescribed in patients with cancer; there is increasing evidence of their effects on cancer development and survival. The objective of this narrative review is to comprehensively identify cancer medications that have clinically meaningful drug–drug interactions (DDIs) with PPIs, including loss of efficacy or adverse effects, and to explore the association between PPIs and cancer.Methods: A PubMed search of English language studies published from 1 January 2016, to 1 June 2021 was conducted. The search terms included “proton pump inhibitors,” “cancer,” “chemotherapy,” “immunotherapy,” “hormonotherapies,” “targeted therapies,” “tyrosine kinase inhibitors,” and “gut microbiome”. Recent and relevant clinical trials, meta-analyses, and reviews were included.Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their impact on cancer survival remains unclear. PPIs may decrease the efficacy of some antineoplastic agents through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate). More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome. PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies but may have a protective effect on the renal system.Discussion/Conclusions: PPIs may interact with the cancer microbiome and the efficacy of various antineoplastic agents, although only a few DDIs involving PPIs are clinically significant. Further pharmaco-epidemiological studies are warranted, but physicians should be aware of the potential consequences of PPI use, which should be dose appropriate and prescribed according to guidelines.

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Section: Resultsmentioning

confidence: 99%

Proton Pump Inhibitors and Cancer: Current State of Play

2022

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Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series

Lau,

van Kesteren,

Cao

et al. 2024

Ann Hematol

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Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

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