title: Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer.
abstract: BACKGROUND
  The relationship between the EGFR gene mutation status and clinical outcome has not fully been assessed in patients with non-small cell lung cancer (NSCLC) who received cytotoxic agents. The aim of this study was to clarify its association. We also examined whether this association could be affected by previous gefitinib treatment.
  
  
  METHODS
  Patients with advanced or postoperative recurrent NSCLC who received both cytotoxic chemotherapy and gefitinib monotherapy in their treatment course were included in this study. An EGFR mutation was determined in exons 19 and 21 by direct sequencing.
  
  
  RESULTS
  Of 194 Japanese patients with advanced or relapsed NSCLC assessable for mutation analysis, 60 received both cytotoxic chemotherapy and gefitinib monotherapy through their treatment courses. EGFR mutations significantly affected progression-free survival (PFS) in the first-line cytotoxic chemotherapy regimens in the multivariate analysis (hazard ratio for PFS = 0.422; p = 0.0422). In contrast, in 28 (47%) of the 60 patients who also received cytotoxic chemotherapy after the relapse to gefitinib monotherapy, there were no differences in PFS stratified by EGFR mutation status. The sensitivity to gefitinib was, however, correlated with EGFR mutation status, and its sensitivity was retained even in the second-line treatment setting in patients with EGFR mutations.
  
  
  CONCLUSIONS
  EGFR mutations were therefore significantly associated with a better PFS in the first-line cytotoxic chemotherapy regimens. However, its association was not observed in the cytotoxic regimens administered after the relapse to gefitinib monotherapy, whereas gefitinib sensitivity was associated with an EGFR mutation even in the second-line or later treatment settings.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, 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: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib