合并使用胃酸抑制药可能会降低吉非替尼疗效: 基于单个肿瘤中心的回顾性研究

doi:10.5246/jcps.2020.03.016

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (3): 192-198.DOI: 10.5246/jcps.2020.03.016

合并使用胃酸抑制药可能会降低吉非替尼疗效: 基于单个肿瘤中心的回顾性研究

郭子寒^1,2#, 杜琼^1,2#, 叶璇^1,2#, 高菲菲^1,2, 尤玉芳^1,2, 余波^3*, 翟青^1,2*

1. 复旦大学附属肿瘤医院药剂科, 上海 200032
2. 复旦大学上海医学院肿瘤学系, 上海 200032
3. 上海交通大学医学院附属同仁医院药剂科, 上海 200336

收稿日期:2019-12-28 修回日期:2020-01-15 出版日期:2020-03-30 发布日期:2020-01-29
通讯作者: Tel.: +86-18017317070, E-mail: zhaiqing63@126.com, Tel.: +86-15821279851, E-mail: miguelboyu@msn.cn

Concomitant administration of gastric acid suppression might attenuates the clinical efficacy of gefitinib: a single cancer center retrospective study

Zihan Guo^1,2#, Qiong Du^1,2#, Xuan Ye^1,2#, Feifei Gao^1,2, Yufang You^1,2, Bo Yu^3*, Qing Zhai^1,2*

1. Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
3. Department of Pharmacy, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China

Received:2019-12-28 Revised:2020-01-15 Online:2020-03-30 Published:2020-01-29
Contact: Tel.: +86-18017317070, E-mail: zhaiqing63@126.com, Tel.: +86-15821279851, E-mail: miguelboyu@msn.cn

摘要/Abstract

摘要：

药物动力学研究表明胃酸抑制药(gastric acid suppression, AS)可以减少吉非替尼的暴露。然而, 这种药物-药物相互作用的临床意义尚未确定。本研究旨在确定真实世界中AS是否会对吉非替尼的临床结果产生影响。随机抽取2016–2018年在我院接受吉非替尼治疗的200名患者进行回顾性分析, 根据是否合并使用AS分为AS组和非AS组, 比较两组患者的临床特征、疗效和不良反应的差异。188名患者符合入排标准, 其中AS组49名, 非AS组139名, AS组和非AS组的ORR分别为69.4% vs 73.4% (P = 0.591), DCR分别为89.8% vs 90.6% (P = 0.0486), PFS分别为9.7个月vs 12.2个月(P = 0.0644), 差异均无统计学意义。进一步的分析结果显示, AS与吉非替尼重叠的时间与PFS相关, 重叠率超过50%的患者, PFS显著降低(8.4个月 vs 12.6个月, P = 0.0004)。两组患者最常见的不良反应为皮疹、肝酶升高和腹泻, 但差异无统计学意义(P值>0.05)。因此AS与吉非替尼联合使用不是绝对的禁忌症, 但应尽可能避免长期联合使用。

关键词: 胃酸抑制药, 吉非替尼, 相互作用, 临床意义

Abstract:

Recent pharmacokinetic studies have demonstrated that gastric acid suppression (AS) reduces exposure of gefitinib. However, the clinical significance of this drug-drug interaction (DDI) has not been determined. We, therefore, evaluated it in this real-world study.A total of200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center (FUSCC) were randomly selected. The patients were divided into two groups according to whether AS was used. The clinical characteristics of the patients were collected, and the efficacy and safety of gefitinib were compared between the two groups. We showed that188 patients were considered eligible for this retrospective analysis, 49 received AS (AS user group), while 139 patients did not (AS non-user group). Objective response rate (ORR) and disease control rate (DCR) in the AS user group versus AS non-user group were 69.4% versus 73.4% (P = 0.591) and 89.8% versus 90.6% (P = 0.486), respectively, while the progression-free survival (PFS) were 9.7 versus 12.2 months (P = 0.0644). No significant difference in ORR, DCR or PFS was observed between the two groups. Further study showed that the PFS was related to the time of co-administration, and the patients receiving over 50% AS prescription overlap with gefitinib was significantly less compared with the other people (8.4 vs 12.6 months, P = 0.0004). The frequencies of rash (8.2% vs 15.1%,P = 0.281), diarrhea (4.1% vs 6.5%, P = 0.539) and elevated ALT or AST level (6.1% vs 10.1%, P = 0.407) were similar for both groups. Therefore, concomitant use of AS and gefitinib might affect the efficacy of gefitinib, which should be avoided if possible.

Key words: Drug interactions, Gastric acid suppression, Gefitinib, Clinical impact

中图分类号:

R975

Supporting:

郭子寒, 杜琼, 叶璇, 高菲菲, 尤玉芳, 余波, 翟青. 合并使用胃酸抑制药可能会降低吉非替尼疗效: 基于单个肿瘤中心的回顾性研究[J]. 中国药学(英文版), 2020, 29(3): 192-198.

Zihan Guo, Qiong Du, Xuan Ye, Feifei Gao, Yufang You, Bo Yu, Qing Zhai. Concomitant administration of gastric acid suppression might attenuates the clinical efficacy of gefitinib: a single cancer center retrospective study[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(3): 192-198.

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合并使用胃酸抑制药可能会降低吉非替尼疗效: 基于单个肿瘤中心的回顾性研究

Concomitant administration of gastric acid suppression might attenuates the clinical efficacy of gefitinib: a single cancer center retrospective study

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