Glucocorticoids may compromise the effect of gefitinib in non-small cell lung cancer.
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.
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan.|Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan.
Hsian-Yu
HY
Wang
Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.
Yu-Ling
YL
Chang
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan.
Chun-Chun
CC
Cheng
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan.
Min-Wu
MW
Chao
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City, Taiwan.|National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
Su-I
SI
Lin
The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan.
Shiow-Lin
SL
Pan
Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.
Chih-Cheng
CC
Hsu
Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
Tsang-Wu
TW
Liu
Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu City, Taiwan.|Miaoli General Hospital, Ministry of Health and Welfare, Miaoli County, Taiwan.
Han-Chin
HC
Cheng
Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan.
Ching-Ping
CP
Tseng
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung City, Taiwan.
Shih-Jen
SJ
Liu
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.|Department of Public Health, China Medical University, Taichung, Taiwan, Taichung City, Taiwan.|Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Hui-Ju
HJ
Tsai
Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.|Institute of Public Health, National Yang-Ming University, Taipei City, Taiwan.
Hsing-Yi
HY
Chang
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan.|Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan.
John T-A
JT
Hsu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice; D008875:Middle Aged; D011799:Quinazolines / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
EGFR; NSCLC; TKI; glucocorticoids; national health insurance research database Taiwan