Department of Pharmacy, Hokkaido University Hospital, Kita 14-jo, Nishi 5-chome, Kita-ku, Sapporo, 060-8648, Japan.
Laboratory of Clinical Pharmaceutics & Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo, 060-0812, Japan.
Eur J Clin Pharmacol. 2021 Mar;77(3):381-388. doi: 10.1007/s00228-020-03013-9. Epub 2020 Oct 7.
Gefitinib is one of the standard treatments for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations. It has been reported that acid suppressants (AS) decrease the anti-tumor effect of gefitinib by reducing its solubility. AS is sometimes necessary in cancer patients; however, previous reports have not shown the most compatible AS with gefitinib administration in cancer patients. This study was conducted to determine if histamine type 2 receptor antagonists (H2RAs) can affect the anti-tumor efficacy of gefitinib.
Eighty-seven patients with NSCLC who were administered gefitinib were retrospectively investigated. Patients who were co-administered H2RA were compared with non-AS control patients. H2RA was administered once a day at about 3-5 or 8-12 h after gefitinib intake. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR), and adverse effects.
Median PFS in H2RA group and control group was 8.0 months and 9.0 months, respectively, with no significant difference (p = 0.82). The incidence of liver dysfunction was significantly less in patients administered H2RA, whereas there were no differences between the two groups with regard to skin toxicity and diarrhea. Multivariate analysis suggested that H2RA co-administration is not a risk factor for worse PFS and OS (hazard ratio of 0.95, 0.86; 95% confidence interval of 0.60-1.48, 0.52-1.43; p = 0.82 and 0.60, respectively).
This study demonstrated that concomitant administration of H2RA with gefitinib does not affect the efficacy of gefitinib.
吉非替尼是表皮生长因子受体突变的非小细胞肺癌（NSCLC）的标准治疗方法之一。据报道，酸抑制剂（AS）通过降低其溶解度来降低吉非替尼的抗肿瘤作用。AS 在癌症患者中有时是必需的；然而，以前的报告并没有显示出与癌症患者吉非替尼给药最兼容的 AS。本研究旨在确定 H2 受体拮抗剂（H2RAs）是否会影响吉非替尼的抗肿瘤疗效。
回顾性调查了 87 例接受吉非替尼治疗的 NSCLC 患者。将接受 H2RA 联合治疗的患者与非 AS 对照组患者进行比较。H2RA 每天一次给药，大约在吉非替尼摄入后 3-5 小时或 8-12 小时。本研究的主要终点是无进展生存期（PFS），次要终点是总生存期（OS）、总缓解率（ORR）和不良反应。
H2RA 组和对照组的中位 PFS 分别为 8.0 个月和 9.0 个月，无显著差异（p=0.82）。接受 H2RA 治疗的患者肝功能障碍发生率显著降低，而两组之间皮肤毒性和腹泻无差异。多变量分析表明，H2RA 联合治疗不是 PFS 和 OS 恶化的危险因素（风险比分别为 0.95、0.86；95%置信区间分别为 0.60-1.48、0.52-1.43；p=0.82 和 0.60）。
本研究表明，H2RA 与吉非替尼同时给药不会影响吉非替尼的疗效。
