A multicenter retrospective study evaluating the effect of proton pump inhibitors on adjuvant tegafur-uracil/leucovorin efficacy for stage II–III colorectal cancer

We hypothesized that there is reduced efficacy of fluorinated pyrimidines, such as capecitabine, caused by low active folic acid levels induced by vitamin B₁₂ deficiency, due to proton pump inhibitors (PPIs), and that this can be recovered by the administration of leucovorin (LV). Thus, we retrospectively analyzed the effects of PPIs on adjuvant tegafur–uracil (UFT) plus LV for stage II/III colorectal cancer (CRC). Patients newly diagnosed with stage II/III CRC who underwent curative surgery and received adjuvant UFT/LV therapy between January 2013 and June 2018 were included. The primary endpoint was the difference in relapse-free survival (RFS) between the PPI and non-PPI groups. Data from 396 eligible patients were evaluated, 84 of whom received PPIs. There were 93 relapse events and 57 deaths across the groups. RFS rates at 5 years were 73.8% (95% confidence interval [CI], 62.9–81.9%) and 77.1% (95% CI, 72.0-81.4%) in the PPI and non-PPI groups, respectively. Cox regression analysis showed no significant differences in RFS between the PPI and non-PPI groups (hazard ratio, 1.16; 95% CI, 0.72–1.87; P = 0.539). Our findings suggest that the concomitant use of PPIs does not significantly reduce the efficacy of adjuvant UFT/LV treatment for patients with stage II/III CRC.