Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study

Wang, Xinchen; Liu, Qing; Hálfdánarson, Óskar; Zoëga, Helga; Sadr–Azodi, Omid; Engstrand, Lars; Fall, Katja; Brusselaers, Nele

doi:10.1038/s41416-021-01480-0

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…This has been demonstrated in both meta-analyses of all patient types and in patients with cancer, specifically breast cancer where the hazard ratio for increased risk for mortality has been estimated at 1.43 (95% confidence interval 1.24-1.47). 2 , 3 , 4 , 5 This effect likely biases the comparison carried out by Del Re et al., and may obfuscate the etiology of this PFS difference as a drug-interaction concern, when it may in fact be driven by PPI use independent of drug interactions. Secondly, the magnitude of reduction in PFS demonstrated is not likely biologically plausible given the purported mechanism suggested for this interaction.…”

mentioning

confidence: 99%

Reply to: Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

et al. 2022

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confidence: 99%

Reply to: Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

et al. 2022

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“…Because bacteria can develop antibiotic resistance, there is interest in evaluating non-antibiotic drugs that have modulating effects on the microbiome in regard to CRC prevention. There are many such drugs that have been shown to influence the development of CRC, including proton pump inhibitors [ 180 ], other non-steroidal anti-inflammatory drugs [ 181 ], and certain antihistamines [ 182 ]. These drugs have also been shown to modulate the microbiome [ 177 , 183 ].…”

Section: Preventative Strategiesmentioning

confidence: 99%

The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer

Tokumaru

et al. 2022

Cancers

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The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research.

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“…If this is a real association, then the potentially worse outcomes in patients treated with capecitabine concomitant with PPI may be explained by the increased risk of mortality due to the PPI alone, rather than a pharmacological interaction between the two drugs. Another large cohort study ( n = 32,411) found that PPI use after colorectal cancer diagnosis was associated not only with increased all-cause mortality (adjusted HR 1.38, 95% CI 1.32–1.44) but also colorectal cancer-specific mortality (adjusted HR 1.34, 95% CI 1.28–1.41), [ 39 ]. Furthermore, long-term use of PPI may also influence the risk of cancer development.…”

Section: Ppi Use and Health Outcomesmentioning

confidence: 99%

Re-thinking the possible interaction between proton pump inhibitors and capecitabine

Jeong

Molloy

Ang

et al. 2022

Cancer Chemother Pharmacol

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Proton Pump Inhibitors (PPI) rank within the top ten most prescribed medications in Europe and USA. A high frequency of PPI use has been reported amongst patients undergoing chemotherapy, to mitigate treatment-induced gastritis or gastro-oesophageal reflux. Several recent, mostly retrospective, observational studies have reported inferior survival outcomes among patients on capecitabine who concomitantly use PPI. Whilst this association is yet to be definitively established, given the prominence of capecitabine as an anti-cancer treatment with multiple indications, these reports have raised concern within the oncological community and drug regulatory bodies worldwide. Currently, the leading mechanism of interaction postulated in these reports has focussed on the pH altering effects of PPI and how this could diminish capecitabine absorption, leading to a decrease in its bioavailability. In this discourse, we endeavour to summarise plausible pharmacokinetic interactions between PPI and capecitabine. We provide a basis for our argument against the currently proposed mechanism of interaction. We also highlight the long-term effects of PPI on health outcomes, and how PPI use itself could lead to poorer outcomes, independent of capecitabine.

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Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study

Cited by 14 publications

References 49 publications

Reply to: Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

Reply to: Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer

Re-thinking the possible interaction between proton pump inhibitors and capecitabine

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