Proton pump inhibitors and cancer treatments: Emerging evidence against coadministration

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL

ACS Catalysis Pub Date : 2024-07-01 DOI:10.1016/j.ctrv.2024.102794

Jean-Luc Raoul , Philip D. Hansten

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Abstract

Background

Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs).

Results

Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib). Relations between microbiota, the immune system, and the efficacy of immunotherapy are now obvious, just as modifications to gut flora after PPIs use are well-known. Many retrospective articles, including articles based on individual-participant data from randomized studies, demonstrated that patients treated with CPIs have a poorer outcome (overall survival, progression-free survival and response rate) when they received PPIs concomitantly, while there was no impact of such coprescription among patients in control arms, not treated with immunotherapies. Similar data were also observed in patients treated with palbociclib.

Conclusion

For these interactions, it is very important to use the precautionary principle and warn patients and physicians about this. In patients who require acid suppression because of severe symptoms, using antacids or H2 blockers could be recommended.

Abstract Image

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质子泵抑制剂与癌症治疗：反对联合用药的新证据。

背景：尽管越来越多的数据显示，质子泵抑制剂（PPIs）会影响主要抗癌药物的疗效，但它们仍被广泛用于癌症患者。这对酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（CPIs）尤为重要：结果：大多数TKIs需要胃酸才能吸收，一些回顾性系列研究表明，联合用药会降低某些TKI（厄洛替尼、吉非替尼和帕唑帕尼）的生存获益。现在，微生物群、免疫系统和免疫疗法疗效之间的关系显而易见，就像使用 PPIs 后肠道菌群的改变一样众所周知。许多回顾性文章（包括基于随机研究中个人参与者数据的文章）都表明，接受 CPIs 治疗的患者如果同时服用 PPIs，其疗效（总生存期、无进展生存期和应答率）会更差，而未接受免疫疗法治疗的对照组患者服用此类药物则没有影响。在接受帕博西尼（palbociclib）治疗的患者中也观察到了类似的数据：对于这些相互作用，使用预防原则并警告患者和医生是非常重要的。对于因症状严重而需要抑酸的患者，建议使用抗酸剂或H2受体阻滞剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.