Yamazaki Tomoko, Uozumi Ryuji, Kawazoe Hitoshi, Kitazume Yoshiko, Iihara Hirotoshi, Fujii Hironori, Takahashi Masaya, Arai Takahiro, Murachi Yasushi, Sato Yumiko, Mikami Takahiro, Hashiguchi Koji, Yoshizawa Tomoe, Takahashi Katsuyuki, Fujita Yukiyoshi, Hosokawa Yuki, Morozumi Issei, Tsuchiya Masami, Yokoyama Atsushi, Hashimoto Hironobu, Furukawa Tetsuya
Department of Pharmacy, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi 320-0834, Japan.
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
J Cancer. 2022 Aug 8;13(10):3073-3083. doi: 10.7150/jca.73385. eCollection 2022.
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 receptor antagonists (HRAs) in early-stage colorectal cancer (CRC) patients using real-world data. 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. In total, 552 patients were included in this study, of which 30 were co-administered HRAs. 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 HRA and non-HRA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of HRAs 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. The study findings suggest that the co-administration of HRAs 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.
卡培他滨的疗效与同时使用胃酸抑制剂之间的关联仍存在争议。我们旨在利用真实世界数据，阐明组胺H受体拮抗剂（HRAs）的联合使用是否会影响早期结直肠癌（CRC）患者使用卡培他滨的疗效。这项多中心、回顾性、观察性研究纳入了2009年1月至2014年12月期间在日本接受卡培他滨单药治疗或CapeOX方案（卡培他滨和奥沙利铂）作为辅助治疗的连续II-III期CRC患者。采用Kaplan-Meier方法估计无复发生存期（RFS）和总生存期。此外，还进行了多变量Cox比例风险模型、倾向评分调整和治疗权重逆概率分析。本研究共纳入552例患者，其中30例同时使用了HRAs。HRA组和非HRA组的五年RFS分别为76.7%（95%置信区间[CI]：57.2-88.1%）和79.8%（95%CI：76.0-83.0%）。多变量Cox比例风险模型和倾向评分调整分析显示，在接受卡培他滨单药治疗的患者中，联合使用HRAs与较差的RFS相关（风险比[HR]分别为2.01；95%CI：0.86-4.70和HR，1.81；95%CI：0.77-4.22）。相比之下，这些结果与接受CapeOX方案的组不一致。研究结果表明，联合使用HRAs可能不会降低早期CRC患者卡培他滨治疗的疗效。为了证实这种关系，需要进行一项采用药代动力学方法的前瞻性研究。
