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Poorer prognosis in Taiwanese female ever smokers with stage IV lung adenocarcinoma who were readministered a tyrosine kinase inhibitor

Authors Yang C, Tsai M, Hung J, Tsai Y, Lee J, Chou S, Liu T, Shen M, Huang M, Chong I

Received 9 November 2015

Accepted for publication 22 January 2016

Published 15 March 2016 Volume 2016:9 Pages 1511—1518

DOI https://doi.org/10.2147/OTT.S100169

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 4

Editor who approved publication: Dr Saad Khan


Chih-Jen Yang,1–4 Ming-Ju Tsai,2 Jen-Yu Hung,2,4 Ying-Ming Tsai,1–3 Jui-Ying Lee,5 Shah-Hwa Chou,5,6 Ta-Chih Liu,7,8 Mei-Chiou Shen,9 Ming-Shyan Huang,2,4,10 Inn-Wen Chong2,6

1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 3Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 5Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 6Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, 7Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 8Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 9Department of Pharmacy, Kaohsiung Medical University Hospital, 10Division of Geriatric Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Background: Readministering a second epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with acquired resistance to an initial EGFR TKI is a common treatment strategy. However, the prognostic factors for the second EGFR TKI are still uncertain. 
Patients and methods:
In this retrospective study, we enrolled patients with stage IV lung adenocarcinoma diagnosed between June 2009 and October 2013 at two university-affiliated hospitals in Taiwan. Basic characteristics including age, sex, smoking status, performance status, EGFR mutation status, tumor response, and progression-free survival (PFS) of the second EGFR TKI (PFS2) were recorded. 
Results:
A total of 72 patients with stage IV adenocarcinoma with susceptible EGFR gene mutations who had been treated with a second EGFR TKI were enrolled. Survival analysis using the Kaplan–Meier method and log-rank test showed a significant difference in PFS2 when classifying the patients according to smoking history and sex (P=0.0179). When stratifying the patients by sex, a significant difference was found in PFS2 between ever smokers and never smokers in the female (1.87 vs 4.87 months, P=0.0081) but not in the male (2.83 vs 2.9 months, P=0.9605) patients. A reduced multivariate model developed using the backward variable selection method showed that only ever smoking remained an independent poor prognostic factor for PFS2, and that sex and ever smoking remained independent poor prognostic factors for PFS2 in the female patients (hazard ratio [HR] =3.386, 95% confidence interval [CI]: 1.015–11.298, P=0.0473).  
Conclusion: This study is the first to demonstrate that female ever smokers have a poorer PFS if they have acquired resistance to an initial EGFR TKI and receive a second EGFR TKI. Further large-scale studies are urgently needed to elucidate the mechanism.

Keywords: lung cancer, adenocarcinoma, epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib, erlotinib, smoker

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