Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell
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PHARMACOKINETICS AND DISPOSITION
Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell lung cancer Yoshitaka Saito 1 & Yoh Takekuma 1 & Masaki Kobayashi 2 & Naofumi Shinagawa 3 & Yasushi Shimizu 4 & Ichiro Kinoshita 4 & Hirotoshi Dosaka-Akita 4 & Ken Iseki 2 & Mitsuru Sugawara 1,5 Received: 1 May 2020 / Accepted: 1 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Gefitinib . Histamine type-2 receptor antagonists (H2RAs) . Acid suppressants (AS) . Antacids . EGFR . Non-small cell lung cancer
Background Gefitinib is one of the most prescribed epidermal growth factor receptor tyrosine kinase inhibitors
(EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC) [1, 2]. It has been reported that these medicines are more effective than cytotoxic anti-cancer agents in patients with EGFR mutations [1, 2]. EGFR
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-03013-9) contains supplementary material, which is available to authorized users. * Mitsuru Sugawara [email protected]
3
First Department of Medicine, Hokkaido University School of Medicine, Kita 15-jo, Nishi 7-chome, Kita-ku, Sapporo 060-8638, Japan
1
Department of Pharmacy, Hokkaido University Hospital, Kita 14-jo, Nishi 5-chome, Kita-ku, Sa
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