title: Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp.
abstract: This study was prospectively designed to evaluate a phase II study of gefitinib for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Clinical samples were tested for EGFR mutations by peptide nucleic acid-locked nucleic acid PCR clamp, and patients having EGFR mutations were given gefitinib 250 mg daily as the second treatment after chemotherapy. Poor PS patients omitted chemotherapy. Of 107 consecutive patients enrolled, samples from 100 patients were informative, and EGFR mutations were observed in 38 patients. Gefitinib was given to 27 patients with EGFR mutations, and the response rate was 78% (one complete response and 20 partial responses; 95% confidence interval: 58-93%). Median time to progression and median survival time (MST) from gefitinib treatment were 9.4 and 15.4 months, respectively. Grade 3 hepatic toxicity and skin toxicity were observed in one patient each. There were significant differences between EGFR mutations and wild-type patients in response rates (78 vs 14%, P = 0.0017), and MST (15.4 vs 11.1 months, P = 0.0135). A Cox proportional hazards model indicated that negative EGFR mutation was a secondary prognostic factor (hazards ratio: 2.259, P = 0.036). This research showed the need for screening for EGFR mutations in NSCLC patients.
authors.affiliation: Department of Respiratory Medicine, Saitama Medical University, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sutani
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Udagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Uchida
authors.forename: N
authors.initials: N
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Miyazawa
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: M
authors.initials: M
authors.lastname: Kanazawa
authors.forename: K
authors.initials: K
authors.lastname: Hagiwara
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
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; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020135:Peptide Nucleic Acids / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D020135:Peptide Nucleic Acids; D011799:Quinazolines; D000077156:Gefitinib