Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab.
背景：在接受贝伐珠单抗治疗的晚期结直肠癌患者中，约三分之一会同时使用质子泵抑制剂或H2受体拮抗剂。然而，关于这两种药物对该类患者影响的研究数据有限。为探究在接受贝伐珠单抗治疗的结直肠癌患者中使用质子泵抑制剂和H2受体拮抗剂的肿瘤学结局，我们利用2005年至2020年台湾全民健康保险研究资料库及台湾癌症登记资料库进行了回顾性队列研究。方法：在接受贝伐珠单抗治疗的结直肠癌患者中，通过1:4倾向评分匹配将质子泵抑制剂使用者和H2受体拮抗剂使用者与未使用抑酸剂的患者进行配对，并以1:1倾向评分对质子泵抑制剂使用者与H2受体拮抗剂使用者进行匹配。根据累计用药剂量将质子泵抑制剂使用者分为四个剂量水平以评估剂量-反应关系。主要研究终点为5年总生存期和癌症特异性生存期。结果：与未使用抑酸剂的患者相比，H2受体拮抗剂使用者和质子泵抑制剂使用者的总生存期均有所降低，其中质子泵抑制剂对总生存期的负面影响更为显著。与H2受体拮抗剂使用者相比，质子泵抑制剂使用者的5年总生存期（调整后风险比：1.19，95%置信区间：1.09–1.31）和癌症特异性生存期（调整后风险比：1.20，95%置信区间：1.09–1.31）均较低。在质子泵抑制剂使用者中观察到5年总生存期和癌症特异性生存期存在类似的剂量-反应关系。结论：在接受贝伐珠单抗治疗的转移性结直肠癌患者中，与使用H2受体拮抗剂相比，质子泵抑制剂的使用与剂量依赖性的不良肿瘤学结局相关。
Proton Pump Inhibitors Worsen Colorectal Cancer Outcomes in Patients Treated with Bevacizumab
肿瘤(癌症)患者之家