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Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study

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Abstract

Purpose

Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine.

Method

A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher’s exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan–Meier method and compared using the log-rank test.

Results

In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61–2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33–2.76, p = 0.93).

Conclusion

No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

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Availability of Data and Material

Yes. Data are available upon request from the study sponsor (University Hospital, Lille) and from the principal investigator Anthony Turpin.

Code Availability

Not applicable.

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Acknowledgements

We would like to thank Séverine Marchant and Editage (www.editage.com) for English language editing. We are also thankful to Antoine de Courrèges and André-Michel Bimbai for their participation in the statistical analyses.

Author information

Authors and Affiliations

  1. University of Lille, Lille, France

    Marie Bridoux

  2. Methodology and Biostatistics Unit, Centre Oscar Lambret, Lille, France

    Marie-Cécile Le Deley & Dienabou Sylla

  3. Medical Oncology Department, Lille University Hospital, Lille, France

    Marie Bridoux & Anthony Turpin

  4. Univ. Lille, CHU Lille, ULR 7365 – GRITA –Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000, Lille, France

    Nicolas Simon

  5. Department of Radiation Oncology, Oscar Lambret Centre, Lille, France

    Xavier Mirabel

  6. University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 - UMR-S 1277 - CANTHER-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, France

    Anthony Turpin

  7. Univ. Lille, CHU Lille, ULR 2694 METRICS, Lille, France

    Nicolas Bertrand

Authors
  1. Marie Bridoux
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  2. Marie-Cécile Le Deley
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  3. Nicolas Bertrand
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  4. Nicolas Simon
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  5. Dienabou Sylla
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  6. Xavier Mirabel
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  7. Anthony Turpin
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Contributions

Marie Bridoux: conceptualization, investigation, writing, reviewing, and editing. Anthony Turpin: conceptualization, supervision, writing, reviewing, and editing. Marie-Cécile Le Deley: methodology, formal analysis, writing, reviewing, and editing. Dienabou Sylla: methodology, formal analysis. Nicolas Simon, Nicolas Bertrand, and Xavier Mirabel: writing, reviewing, and editing.

Corresponding author

Correspondence to Anthony Turpin.

Ethics declarations

Ethics Approval

The ethics committee of the participating center approved the study and follow-up protocol.

Consent to Participate

Alive patients were given a no opposition letter according to French regulations. A derogation was allowed for deceased patients.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no competing interests.

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Bridoux, M., Le Deley, MC., Bertrand, N. et al. Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study. J Gastrointest Canc 54, 545–553 (2023). https://doi.org/10.1007/s12029-022-00825-z

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  • DOI: https://doi.org/10.1007/s12029-022-00825-z

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