Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study Group experience

• Published in: Journal of cancer research and clinical oncology 2009, Vol.135 (1), p.117-123
• Main Authors: Hotta, Katsuyuki, Kiura, Katsuyuki, Takigawa, Nagio, Kuyama, Shoichi, Segawa, Yoshihiko, Yonei, Toshiro, Gemba, Kenichi, Aoe, Keisuke, Shibayama, Takuo, Matsuo, Keisuke, Kamei, Haruhito, Fujiwara, Yoshiro, Bessho, Akihiko, Moritaka, Tomonori, Sugimoto, Keisuke, Tabata, Masahiro, Ueoka, Hiroshi, Tanimoto, Mitsune
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - secondary; Chemotherapy; Clinical outcomes; Female; Gender differences; Hematology; Humans; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Oncology; Original Paper; Pharmacology. Drug treatments; Pneumology; Prognosis; Protein Kinase Inhibitors - therapeutic use; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Sex Factors; Smoking; Smoking - epidemiology; Survival Rate; Tobacco, tobacco smoking; Toxicology; Treatment Outcome; Tumors of the respiratory system and mediastinum
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-008-0431-1

Background Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma. Methods We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy (250 mg/day), and whose smoking status was known. Tumour response and survival were evaluated and stratified by smoking status and gender. Results Among the 260 patients, 157 were male (60%). Median pack-years was 40 (range 8-160) and 23 (range 1-74) in male and female smokers, respectively. Objective response was observed in 62 (23.8%) of the 260 patients, and 1-year overall survival and progression-free survival were 45.1 and 24.3%, respectively. Multivariate analysis revealed that smoking status (pack-years) was an independent predictive factor for response to gefitinib [odds ratio (OR) = 0.971, 95% confidence interval (CI) = 0.947-0.995; P = 0.0159] in male patients, but not in female patients (OR = 0.999, 95%CI = 0.957-1.042). Additionally, pack-years significantly influenced the overall survival in males (hazard ratio = 1.010; 95%CI = 1.002-1018, P = 0.0169), while differential survival of females was not significantly predicted by this factor (P = 0.7639). Conclusions In male patients with lung adenocarcinoma, cumulative smoking significantly affected response and survival following gefitinib treatment, while in female patients, responsiveness to gefitinib was independent of smoking status. These results suggest that the influence of smoking habit on responsiveness to gefitinib is gender specific.