title: Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403).
abstract: The purpose of this study was to evaluate the efficacy of gefitinib and the feasibility of screening for epidermal growth factor receptor (EGFR) mutations among select patients with advanced non-small cell lung cancer (NSCLC). Stage IIIB/IV NSCLC, chemotherapy-naive patients or patients with recurrences after up to two prior chemotherapy regimens were eligible. Direct sequencing using DNA from tumour specimens was performed by a central laboratory to detect EGFR mutations. Patients harbouring EGFR mutations received gefitinib. The primary study objective was response; the secondary objectives were toxicity, overall survival (OS), progression-free survival (PFS), 1-year survival (1Y-S) and the disease control rate (DCR). Between March 2005 and January 2006, 118 patients were recruited from 15 institutions and were screened for EGFR mutations, which were detected in 32 patients--28 of whom were enrolled in the present study. The overall response rate was 75%, the DCR was 96% and the median PFS was 11.5 months. The median OS has not yet been reached, and the 1Y-S was 79%. Thus, gefitinib chemotherapy in patients with advanced NSCLC harbouring EGFR mutations was highly effective. This trial documents the feasibility of performing a multicentre phase II study using a central typing laboratory, demonstrating the benefit to patients of selecting gefitinib treatment based on their EGFR mutation status.
authors.affiliation: Outpatients Treatment Center, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ketamura@ncc.go.jp
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: I
authors.initials: I
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Kashii
authors.forename: S
authors.initials: S
authors.lastname: Negoro
authors.forename: T
authors.initials: T
authors.lastname: Hirashima
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: Y
authors.initials: Y
authors.lastname: Ichinose
authors.forename: N
authors.initials: N
authors.lastname: Ebi
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: N
authors.initials: N
authors.lastname: Katakami
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Fukuoka
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib