Generic placeholder image

Clinical Cancer Drugs

Author(s): Wang Chun Kwok, James Chung Man Ho, David Chi Leung Lam, Macy Mei Sze Lui, Mary Sau Man Ip and Terence Chi Chun Tam*

DOI: 10.2174/2212697X06666191021155535

DownloadDownload PDF Flyer Cite As
Clinical Impact of Gastric Acid Suppressants Use on the Efficacy of Gefitinib in Patients with Advanced Adenocarcinoma of the Lung Harboring Common EGFR Mutations

Page: [57 - 61] Pages: 5

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: Gefitinib was approved by the Food and Drug Administration (FDA) of the United States (US) for the treatment of advanced non-small cell carcinoma harboring sensitizing epidermal growth factor receptor (EGFR) mutations. The use of gastric acid-suppressing medication inhibits gefitinib absorption and reduces its plasma concentration, but retrospective studies on whether there is the corresponding repercussion on progression-free survival (PFS) have yielded variable results, mainly due to heterogeneity in study cohorts and study designs.

Objectives: To assess the clinical impact of the use of gastric acid-suppressing medication in patients on first-line gefitinib for NSLC harboring common EGFR mutation.

Methods: This is a retrospective cohort study conducted in a single, tertiary referral center in Hong Kong S.A.R., which included 193 Chinese patients with advanced adenocarcinoma of lung harboring common sensitizing EGFR mutations who received gefitinib as the first-line treatment. The progression- free survival (PFS) and overall survival (OS) for patients who took gastric acid-suppressing agents, namely histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI), were compared with those who did not take such medication (control group).

Results: Despite the universal practice to separate the medicating time of gastric acid suppressants and EGFR-TKIs by 12 hours, patients who were on gastric acid suppressants had significantly shorter PFS, especially for those on proton pump inhibitor (Median 368 vs. 189 vs. 166 days - For control, H2RA group and PPI group respectively, p-value <0.001). The OS is also significantly shorter for those taking gastric acid suppressants (Median 825 vs. 485 vs. 422 days - For control, H2RA group and PPI group respectively, p-value <0.001).

Conclusion: The co-administration of gastric acid suppressants with gefitinib is associated with shorter progression-free survival and overall survival.

Keywords: Lung cancer, EGFR-TKI, gastric-acid suppressing agents, survival, gefitinib, EGFR mutations.

Graphical Abstract

[1]
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361(10): 947-57.
[http://dx.doi.org/10.1056/NEJMoa0810699] [PMID: 19692680]
[2]
Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37(Suppl. 8): S4-S66.
[http://dx.doi.org/10.1016/S0959-8049(01)00267-2] [PMID: 11602373]
[3]
Smelick GS, Heffron TP, Chu L, et al. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development. Mol Pharm 2013; 10(11): 4055-62.
[http://dx.doi.org/10.1021/mp400403s] [PMID: 24044612]
[4]
Cohen MH, Williams GA, Sridhara R, et al. United states food and drug administration drug approval summary: Gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 2004; 10(4): 1212-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0564] [PMID: 14977817]
[5]
Yokota H, Sato K, Okuda Y, et al. Effects of histamine 2-receptor antagonists and proton pump inhibitors on the pharmacokinetics of gefitinib in patients with non-small-cell lung cancer. Clin Lung Cancer 2017; 18(6): e433-9.
[http://dx.doi.org/10.1016/j.cllc.2017.05.010] [PMID: 28579188]
[6]
Yasumuro O, Uchida S, Kashiwagura Y, et al. Changes in gefitinib, erlotinib and osimertinib pharmacokinetics under various gastric pH levels following oral administration of omeprazole and vonoprazan in rats. Xenobiotica 2017; 1-7.
[PMID: 29057719]
[7]
Nieves Sedano M, Manuel Caro Teller J, García Muñoz C, et al. Clinical impact of gastric acid suppressing medication on the effectiveness of tyrosine kinase inhibitors in lung cancer patients. J BUON 2018; 23(3): 647-53.
[PMID: 30003732]
[8]
Kumarakulasinghe NB, Syn N, Soon YY, et al. EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: A retrospective database analysis of potential drug interaction. Oncotarget 2016; 7(51): 85542-50.
[http://dx.doi.org/10.18632/oncotarget.13458] [PMID: 27907909]
[9]
Zenke Y, Yoh K, Matsumoto S, et al. Clinical impact of gastric acid-suppressing medication use on the efficacy of erlotinib and gefitinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations. Clin Lung Cancer 2016; 17(5): 412-8.
[http://dx.doi.org/10.1016/j.cllc.2016.01.006] [PMID: 26944770]
[10]
Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004; 304(5676): 1497-500.
[http://dx.doi.org/10.1126/science.1099314] [PMID: 15118125]
[11]
Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350(21): 2129-39.
[http://dx.doi.org/10.1056/NEJMoa040938] [PMID: 15118073]
[12]
Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: A systematic review and evidence-based clinical practice guideline. J Neurooncol 2010; 96(1): 103-14.
[http://dx.doi.org/10.1007/s11060-009-0057-4] [PMID: 19957014]