Drug-Drug Interactions with Proton Pump Inhibitors in Cancer Patients - an Underrecognized Cause of Treatment Failure

Sep 24, 2026

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Drug-drug interactions between proton pump inhibitors (PPIs) and anticancer therapies may contribute to preventable treatment failures in oncology. PPIs are widely prescribed for digestive symptoms and often used inappropriately, while long-term acid suppression can reduce absorption of targeted agents such as TKIs and alter the gut microbiome. These effects may lower efficacy of specific TKIs and potentially suppress benefits from immune checkpoint inhibitors. Evidence also remains inconsistent for several oral drugs, prompting a precautionary approach and careful prescribing.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Introduction

Literature Search Strategy

Mechanisms of Drug-Drug Interactions of PPIs with Anticancer Treatments

REVIEW Drugedrug interactions with proton pump inhibitors in cancer patients: an underrecognized cause of treatment failure J. L. Raoul1*, C. Moreau-Bachelard1, M. Gilabert2y, J. Edeline3 & J. S. Frénel1 1Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Saint-Herblain, France; 2Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 3Department of Medical Oncology, Centre Eugène Marquis, Rennes, France Available online 8 February 2023 New concepts and drugs have revolutionized medical treatment for cancers. These drugs, which are very expensive and usually well tolerated, have dramatically improved cancer prognosis. We must use them wisely for patients to fully beneﬁt. Gastric acid antisecretory drugs and particularly proton pump inhibitors (PPIs) revolutionized the treatment of gastroduodenal ulcers and severe gastroesophageal reﬂux, but are frequently overused for symptomatic treatment of epigastric pain or heartburn. Long-term acid suppression may alter the efﬁcacy of many anticancer drugs, such as tyrosine kinase inhibitors (TKIs), cyclin-dependent kinase (CDK) 4/6 inhibitors and immune checkpoint inhibitors (ICIs), by either decreasing gastric acid secretion and thus drug absorption, or by modifying the gut microbiome that modulates the response to ICIs. Oncologists thus need to pay particular attention to the concomitant use of PPIs and anticancer drugs. These interactions translate into major clinical impacts, with demonstrated loss of efﬁcacy for some TKIs (erlotinib, geﬁtinib, pazopanib), and conﬂicting results with many other oral drugs, including capecitabine and CDK 4/6 inhibitors. Furthermore, the profound changes in the gut microbiome due to using PPIs have shown that the beneﬁt of using ICIs may be suppressed in patients treated with PPIs. As the use of PPIs is not essential, we must apply the precautionary principle. The ﬁrst sentence of a recent Comment in Nature was “Every day, millions of people are taking medications that will not help them”. We fear that every day millions of cancer patients are taking medications that harm them. While this may well be only association and not causation, there is enough to make us pause until we reach a clear answer. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician. Key words: proton pump inhibitors, tyrosine kinase inhibitors, immune checkpoint inhibitors, chemotherapy drugs, drugedrug interactions, efﬁcacy INTRODUCTION In the past 20 years, the therapeutic landscape in medical oncology has been dramatically modiﬁed by the demonstrated efﬁcacy of both targeted therapies, in many tumors with driver molecular alterations [mainly tyrosine kinase inhibitors (TKIs), taken orally], and immune checkpoint inhibitors (ICIs), in different cancers. These efﬁcient new treatments have a totally different safety proﬁle in common, better than conventional systemic chemotherapy, a higher price plus the possibility of therapeutic failures due to unusual drugedrug interactions.1,2 *Correspondence to: Prof. Jean-Luc Raoul, Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Bd Jean Monod, 44805 Saint-Herblain, France. Tel: þ33-240-679-993 E-mail: [jean-luc.raoul@ico.unicancer.fr](jean-luc.raoul@ico.unicancer.fr) (J. L. Raoul). yDeceased. 2059-7029/© 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). Proton pump inhibitors (PPIs) are some of the most frequently prescribed drugs in the world and frequently prescribed inappropriately to relieve digestive symptoms.3 They are considered very safe, but in the general population, there

FAQs

Why might proton pump inhibitors reduce the effectiveness of anticancer drugs?

Long-term acid suppression can decrease gastric drug absorption and alter the gut microbiome, which influences responses to immunotherapy.

Which anticancer treatments have demonstrated reduced efficacy when used with PPIs?

Some tyrosine kinase inhibitors, including erlotinib, gefitinib, and pazopanib, have shown loss of efficacy with concomitant PPI use.

What does the review recommend regarding PPI prescribing in cancer patients?

Because PPIs are often not essential, the review urges using the precautionary principle, avoiding inappropriate prescriptions, and explaining interaction risks to patients and clinicians.

Sep 24, 2026

Uploaded by Logic