School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sci Rep. 2022 Apr 29;12(1):7002. doi: 10.1038/s41598-022-10938-x.
Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI's bioavailability. Therefore, we aimed to investigate the effects of these drug-drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42-1.76), 1.37 on TTNT (95% CI 1.24-1.52); in the erlotinib was 1.54 on OS (95% CI 1.30-1.82) and 1.19 on TTNT (95% CI 1.01-1.39). Concurrent use of PPIs with first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT in patients with lung adenocarcinoma harboring EGFR mutations.
吉非替尼和厄洛替尼是晚期非小细胞肺癌的一线酪氨酸激酶抑制剂（TKI）。然而，质子泵抑制剂（PPI）或组胺-2 受体拮抗剂（H2RA）与这些药物的联合使用可能会降低 TKI 的生物利用度。因此，我们旨在研究这些药物-药物相互作用的影响。我们调查了 2010 年 1 月 1 日至 2018 年 12 月 30 日期间全国范围内的基于人群的数据库。确定了接受一线吉非替尼或厄洛替尼治疗的晚期肺腺癌新诊断患者。评估了 PPI 或 H2RA 与联合应用吉非替尼或厄洛替尼之间对总生存期（OS）和下一次治疗时间（TTNT）的影响。如果 PPI 或 H2RA 的使用期与 TKI 重叠时间≥20%，则将其定义为 PPI 或 H2RA 用户。共纳入 4340 例吉非替尼和 1635 例厄洛替尼使用者。与 H2RA 组和非使用者组相比，PPI 组的中位 OS 和 TTNT 最短（在吉非替尼队列中：OS：14.35 比 17.67 比 21.87 个月；P<0.0001，TTNT：8.47 比 10.78 比 10.33 个月；P<0.0001）；（在厄洛替尼队列中：OS：16.97 比 20.07 比 23.92 个月；P<0.0001，TTNT：9.06 比 11.85 比 10.90 个月；P=0.0808）。与非使用者组相比，吉非替尼 PPI 组的调整后的危害比（aHR）在 OS 方面为 1.58（95%CI 1.42-1.76），在 TTNT 方面为 1.37（95%CI 1.24-1.52）；在厄洛替尼中，OS 为 1.54（95%CI 1.30-1.82），TTNT 为 1.19（95%CI 1.01-1.39）。在携带 EGFR 突变的肺腺癌患者中，一线吉非替尼或厄洛替尼治疗联合使用 PPI 与较差的 OS 和 TTNT 相关。
