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 pathological 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 radiochemotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. 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 histological response was 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: There is a trend to a lower complete histological response with PPI co-medication 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.