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Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell lung cancer

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Title: Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell lung cancer
Authors: Saito, Yoshitaka Browse this author
Takekuma, Yoh Browse this author →KAKEN DB
Kobayashi, Masaki Browse this author →KAKEN DB
Shinagawa, Naofumi Browse this author
Shimizu, Yasushi Browse this author
Kinoshita, Ichiro Browse this author
Dosaka-Akita, Hirotoshi Browse this author
Iseki, Ken Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Keywords: Gefitinib
Histamine type-2 receptor antagonists (H2RAs)
Acid suppressants (AS)
Non-small cell lung cancer
Issue Date: 7-Oct-2020
Publisher: Springer
Journal Title: European Journal of Clinical Pharmacology
Volume: 77
Start Page: 381
End Page: 388
Publisher DOI: 10.1007/s00228-020-03013-9
PMID: 33029650
Abstract: Purpose 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. Methods 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. Results 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). Conclusion This study demonstrated that concomitant administration of H2RA with gefitinib does not affect the efficacy of gefitinib.
Rights: This is a post-peer-review, pre-copyedit version of an article published in European Journal of Clinical Pharmacology. The final authenticated version is available online at:
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 満

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