title: EGFR mutation of tumor and serum in gefitinib-treated patients with chemotherapy-naive non-small cell lung cancer.
abstract: BACKGROUND
  The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor (EGFR) mutation status.
  
  
  METHODS
  Japanese chemotherapy-naive NSCLC patients were enrolled. They had measurable lesions, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ and bone marrow function. Patients received 250 mg of oral gefitinib daily. EGFR mutations in exon 18, 19, and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence.
  
  
  RESULTS
  All 30 patients were eligible for the assessment of efficacy and safety. An objective response and stable disease were observed in 10 patients (33.3%) and nine patients (30.0%), respectively. The median time to progression was 3.3 months and the median overall survival was 10.6 months. The 1-year survival rate was 43.3%. Grade 3 toxicities were observed in seven patients. EGFR mutation was observed in four of 13 (30.8%) tumors, and two of them achieved partial response. In serum samples, three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib. EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment samples from patients with a partial response or stable disease than in those from patients with progressive disease (p = 0.006).
  
  
  CONCLUSIONS
  Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active, with acceptable toxicities. These results warrant further evaluation of gefitinib monotherapy as a first-line therapy. The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment.
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Ishikawa, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasahara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shibata
authors.forename: Takashi
authors.initials: T
authors.lastname: Sone
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshimoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Waseda
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shiarasaki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ishiura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Nakatsumi
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kashii
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics; D004247:DNA / Q000097:blood*; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D004247:DNA; D066246:ErbB Receptors; D000077156:Gefitinib