title: Clinical factors affecting acquired resistance to gefitinib in previously treated Japanese patients with advanced nonsmall cell lung cancer.
abstract: BACKGROUND
  The risk factors for the development of acquired resistance in nonsmall cell lung cancer (NSCLC) patients responding to gefitinib are unclear. The current study assessed clinicopathologic factors affecting acquired resistance to gefitinib in previously treated patients with advanced NSCLC.
  
  
  METHODS
  Between 2000 and 2004, 197 consecutive Japanese patients with advanced NSCLC underwent treatment with gefitinib. Of these patients, 56 who had continued gefitinib treatment without disease progression for at least 6 months were included in the study.
  
  
  RESULTS
  At a median follow-up time of 21.6 months (range, 7.7-59.7 months), the median time to disease progression was 19.5 months, with progression-free survival rates of 68.5% at 1 year, 33.6% at 2 years, and 21.2% at 3 years. In a multivariate analysis using a Cox regression model, baseline brain metastasis was the strongest prognostic factor affecting acquired resistance to gefitinib (hazards ratio, 2.14; 95% confidence interval, 1.10- 4.17 [P = .025]). In addition, a decreased baseline hemoglobin level (P = .074) and the administration of >1 chemotherapy regimen before gefitinib treatment (P = .069) tended to be significant negative prognostic factors.
  
  
  CONCLUSIONS
  In patients undergoing treatment with gefitinib, the presence of brain metastasis was strongly associated with the emergence of acquired resistance in the current series of NSCLC patients. The finding requires confirmation in a large cohort of patients with advanced NSCLC, including a non-Japanese/Asian population.
authors.affiliation: Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. ysegawa@shikoku-cc.go.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tetsu
authors.initials: T
authors.lastname: Shinkai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib