Clinical factors affecting acquired resistance to gefitinib in previously treated Japanese patients with advanced nonsmall cell lung cancer

Yoshihiko Segawa, Katsuyuki Hotta, Shigeki Umemura, Yoshiro Fujiwara, Tetsu Shinkai, Hiroshi Ueoka, Nagio Takigawa, Masahiro Tabata, Katsuyuki Kiura, Mitsune Tanimoto

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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.

Original languageEnglish
Pages (from-to)1866-1872
Number of pages7
Issue number8
Publication statusPublished - Oct 15 2006



  • Acquired resistance
  • Epidermal growth factor receptor
  • Gefitinib
  • Nonsmall cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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