PPIs Could Be Bad News for Oral Cancer Therapies

Brandon May

July 13, 2021

A substantial proportion of patients with cancer use proton pump inhibitors (PPIs), and up to one-third of these patients are also using oral cancer treatments that could be adversely affected by concomitant PPI use, according to a cross-sectional analysis.

Amit Patel, MD, a gastroenterologist with Duke University, Durham, N.C., was not involved in the study but commented on it in an interview. The "sobering" study findings highlight the need for "clinicians to carefully and regularly assess the indications and need for PPI, which are often overutilized, and consider 'deprescribing' based on clinical guidance," he explained.

Previous research indicates the use of PPIs can lower the bioavailability and efficacy of oral cancer treatments, such as tyrosine kinase inhibitors (TKIs) and checkpoint inhibitors. In the current study, published in JAMA Network Open, researchers sought to identify how many patients with cancer were taking treatments at risk for altered efficacy from PPI use and what factors were associated with use of PPIs.

The Study Findings

Jean-Luc Raoul, MD, and colleagues, analyzed physician-reported medical data of 566 women and 306 men with cancer from four comprehensive cancer centers in France, with a median age of 63 years. A total of 229 patients in the study (26.3%) were taking PPIs.

Most patients (71.1%) were using PPIs on a regular basis; reasons included epigastric pain (50.0%), retrosternal pain (14.0%), proven esophageal or gastric ulcer (8.0%), or gastroprotection (15.0%).

Factors associated with PPI use in this cohort included older age (odds ratio, 1.02; P <.001), Eastern Cooperative Oncology Group performance status (PS) (PS 1: OR, 1.92; PS 2: OR, 2.51; PS 3: OR, 2.33; P <.001), receipt of hormone therapy (OR, 0.59; P =.01), metastatic stage (P =.03), and tumor site (P =.045).

Older age and PS are particularly important characteristics, explained Patel. "Unfortunately, older patients with cancer and/or poor PS are more likely to have medical interactions that may result in their being prescribed PPI medications, often for indications that may not justify their use, and/or for indefinite durations."

He noted that clinicians who are considering prescribing PPI medications should carefully address the indications for PPIs in the clinical scenario, the evidence supporting PPI use for the indication, ratio of benefits and risks, and potential alternatives to PPI use to mitigate potential issues with other therapies.

Approximately 29% of patients who took drugs whose efficacy might be affected by PPI use were also taking other medications, including capecitabine (n = 5), sunitinib (n = 5), cabozantinib (n = 2), pazopanib (n = 1), gefitinib (n = 1), erlotinib (n = 1), and sorafenib (n = 1). Another 39 out of 90 patients (25.6%) taking PPIs were also receiving checkpoint inhibitors. Of the 20 patients who took TKIs and PPIs, a total of 16 reported long-term PPI use. The most common reason for long-term use of PPIs was related to epigastric pain (n = 11).

Since this study was based on physician-reported data, the analysis was limited by the lack of data for all patients seen by each participating physician. In spite of this limitation, the investigators reported no sources of major bias and suggested the study's prospective nature and relatively

PPI Use and Cancer Care

Although issues exist with PPIs in respect to cancer therapies, there are some strategies which may help reduce possible negative effects, Patel said. "When PPI medications are prescribed, they should be used at the lowest effective dose for the shortest necessary duration, and their use should be regularly reevaluated for dose reduction and/or potential discontinuation."

Patel noted that, based on the indication for PPIs, alternatives to PPIs should be considered in the setting of potential drug-drug interactions that may affect the efficacy of oral cancer therapies. "For example, for intermittent typical reflux symptoms such as heartburn, over-the-counter antacids may be considered, along with reflux lifestyle medications," he explained.

Likewise, the study authors stated in their research letter that "PPIs should be actively identified and substituted" in certain cases. The authors added that antacids are also the best option for patients taking checkpoint inhibitors.

"For those patients who absolutely must take TKI and PPI, clinicians can also consider staggering the dosing schedule, such as taking the TKI in the morning at least 2 hours before PPI and/or with an acidic beverage," added Patel.

Although the findings from this study raise potential concerns, Patel stated further clinical investigations are needed to help the medical community better understand the specific effects of PPIs on the efficacy of various chemotherapeutic agents and to also help develop better management options for patients in these settings.

The authors reported relationships with Bayer, Merck, Transgene, and others. Patel has no relevant conflicts of interest to report.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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