Association between the Co-administration of Histamine H2 Receptor Antagonists and the Effectiveness of Capecitabine in Patients with Colorectal Cancer: Propensity Score Analysis

Tomoko Yamazaki, Ryuji Uozumi, Hitoshi Kawazoe, Yoshiko Kitazume, Hirotoshi Iihara, Hironori Fujii, Masaya Takahashi, Takahiro Arai, Yasushi Murachi, Yumiko Sato, Takahiro Mikami, Koji Hashiguchi, Tomoe Yoshizawa, Katsuyuki Takahashi, Yukiyoshi Fujita, Yuki Hosokawa, Issei Morozumi, Masami Tsuchiya, Atsushi Yokoyama, Hironobu HashimotoTetsuya Furukawa

Research output: Contribution to journalArticlepeer-review

Abstract

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 H2 receptor antagonists (H2RAs) 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 H2RAs. 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 H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs 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 H2RAs 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.

Original languageEnglish
Pages (from-to)3073-3083
Number of pages11
JournalJournal of Cancer
Volume13
Issue number10
DOIs
Publication statusPublished - 2022

Keywords

  • capecitabine
  • CapeOX
  • colorectal cancer
  • drug-drug interaction
  • histamine H2 receptor antagonist

ASJC Scopus subject areas

  • Oncology

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