Association between the Co-administration of Histamine H(2) Receptor Antagonists and the Effectiveness of Capecitabine in Patients with Colorectal Cancer: Propensity Score Analysis

Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H(2) receptor antagonists (H(2)RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H(2)RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H(2)RA and non-H(2)RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H(2)RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions: The study findings suggest that the co-administration of H(2)RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.