title: 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.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan, khotta@md.okayama-u.ac.jp.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yonei
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Takuo
authors.initials: T
authors.lastname: Shibayama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsuo
authors.forename: Haruhito
authors.initials: H
authors.lastname: Kamei
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Bessho
authors.forename: Tomonori
authors.initials: T
authors.lastname: Moritaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib