Proton Pump Inhibitors and Capecitabine Efficacy

To the Editor Based on a secondary analysis of the TRIO-013/LOGiC trial, Chu and colleagues recently reported an association between concomitant use of proton pump inhibitors (PPIs) and capecitabine efficacy in patients with advanced gastroesophageal cancer. In patients with gastroesophageal cancer receiving capecitabine and oxaliplatin, PPI users had significantly poorer median progression-free survival, 4.2 vs 5.7 months (hazard ratio, 1.55; 95% CI, 1.29-1.81; P < .001); median overall survival, 9.2 vs 11.3 months (hazard ratio, 1.34; 95% CI, 1.06-1.62; P = .04), and disease control rate (71.2% vs 82.5%; P = .02) vs PPI nonusers. The PPI users were defined as patients whose PPI prescription overlapped with capecitabine plus oxaliplatin treatment duration by at least 20% of the time. However, the authors did not provide any information about the definition of the PPI nonusers, which warrants further consideration. The PPI nonusers may be defined either as patients whose PPI prescription overlapped with capecitabine plus oxaliplatin treatment duration by less than 20% of the time or as patients who did not take PPI at baseline and during the trial, like the previous analyses. If the first definition was used, a proportion of patients who took PPI at baseline and during the trial with a duration less than 20% of study time would be identified as the PPI nonusers, which is irrational and inappropriate. As such, the effect of concomitant use of PPIs on the anticancer efficacy of capecitabine may have been underestimated.

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