In Reply We thank these authors for their interest in our article. It is true that this definition of 20% or more concurrent overlap might have led to an apparent decrease in capecitabine-proton pump inhibitor (PPI) effect, but we were more willing to accept finding a PPI effect and underestimating the interaction than to miss the interaction entirely, for 2 reasons. First, we do not believe that taking a PPI for 3 days (<20%) out of 14 days of capecitabine administration would have clinically meaningful effects. Furthermore, for brevity in the original article, we did not specify that almost all patients identified as having less than 20% concurrent PPI and capecitabine exposure had in fact never taken a PPI. Second, we have successfully used this definition of concurrent use for other PPI-focused oncology studies1-3—for continuity, we continued this definition in this study. We found similar concerning results with patients receiving concurrent PPIs and adjuvant capecitabine in patients with colon cancer, for whom 5-year recurrence-free survival was 74% vs 83% in those not receiving a PPI (P = .03).3
Chu MP, Sawyer MB. Factors Affecting the Association of Proton Pump Inhibitors and Capecitabine Efficacy in Advanced Gastroesophageal Cancer—Reply. JAMA Oncol. 2018;4(2):265. doi:10.1001/jamaoncol.2017.3410
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