Glucocorticoids may compromise the effect of gefitinib in non-small cell lung cancer

// Hsian-Yu Wang 1, 2 , Yu-Ling Chang 3 , Chun-Chun Cheng 4 , Min-Wu Chao 4 , Su-I Lin 5, 6 , Shiow-Lin Pan 4 , Chih-Cheng Hsu 3 , Tsang-Wu Liu 7 , Han-Chin Cheng 8, 9 , Ching-Ping Tseng 2 , Shih-Jen Liu 6, 10 , Hui-Ju Tsai 11, 12, 13 , Hsing-Yi Chang 3, 14 , John T.-A. Hsu 1, 2 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 2 Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan 3 Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan 4 The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan 5 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City, Taiwan 6 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan 7 Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan 8 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu City, Taiwan 9 Miaoli General Hospital, Ministry of Health and Welfare, Miaoli County, Taiwan 10 Graduate Institute of Immunology, China Medical University, Taichung City, Taiwan 11 Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan 12 Department of Public Health, China Medical University, Taichung, Taiwan, Taichung City, Taiwan 13 Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 14 Institute of Public Health, National Yang-Ming University, Taipei City, Taiwan Correspondence to: Hsing-Yi Chang, email: hsingyi@nhri.org.tw John T.-A. Hsu, email: tsuanhsu@nhri.org.tw Keywords: NSCLC, EGFR, TKI, glucocorticoids, national health insurance research database taiwan Received: July 28, 2016 Accepted: October 29, 2016 Published: November 07, 2016 ABSTRACT The epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitors (TKIs) have shown remarkable benefits in non-small cell lung cancer (NSCLC) patients with drug-sensitive mutations in the EGFR gene. Responsive patients are usually continuously prescribed with TKIs until disease progression. Glucocorticoids (GCs) are potent homeostasis maintaining drugs and are frequently used in cancer patients to alleviate discomforts caused by anti-cancer therapies. Several previous studies reported that concomitant use of GCs may compromise the efficacy of chemo-therapeutics in patients with solid tumors. Little is known in the concomitant use of target therapy with GCs in treating NSCLC. In this study, we hypothesized that concomitant use of GCs in EGFR-TKI therapy may be detrimental and addressed this issue using cell cultures and xenograft studies followed by a retrospective population study based on data from the Taiwan national health insurance system. In cell cultures and xenograft studies, GCs were shown to unequally compromise the anti-cancer efficacy of TKIs in both PC9 and NCI-H1975 NSCLC cells models. In the retrospective population study, patients with similar disease status that were co-medicated with GCs had a significantly higher risk of disease progression.