title: Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy.
abstract: OBJECTIVE
  Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy.
  
  
  METHODS
  Genomic DNA was extracted from tumor specimens and EGFR mutations in exons 19 and 21 analyzed by direct sequencing. Patients with stage III/IV NSCLC whose tumors had the EGFR mutations received gefitinib (250 mg/day orally). Response, toxicity and survival data were assessed.
  
  
  RESULTS
  From November 2004-May 2006, 21 patients with EGFR mutations received gefitinib (median age: 59 years; 17 females; 19 non-smokers; all had adenocarcinomas). Two patients discontinued gefitinib and withdrew from the study 3 weeks after gefitinib initiation (interstitial pneumonitis, 1 patient; facial acne, 1 patient). Of 19 patients, 3 achieved complete response, 13 exhibited partial response and 3 had stable disease. Response and disease control rates were 76% (95% confidence interval [CI] 53-92) and 90% (95% CI 70-99), respectively. The most common adverse event was skin toxicity (67%); however, no grade 4 skin toxicities were seen. Ten patients relapsed and three died at a median follow-up period of 12.6 months (range 5.6-23.8 months); median progression-free survival was 12.9 months.
  
  
  CONCLUSIONS
  Analysis of tumor EGFR mutations in patients with NSCLC could be used to identify patients suitable for treatment with gefitinib to obtain optimum response and disease control rates.
authors: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, and Department of Respiratory Medicine, National Nishigunma Hospital, Japan. nsunaga@showa.gunma-u.ac.jp
authors: Noriaki
authors: N
authors: Sunaga
authors: Yoshio
authors: Y
authors: Tomizawa
authors: Noriko
authors: N
authors: Yanagitani
authors: Hironobu
authors: H
authors: Iijima
authors: Kyoichi
authors: K
authors: Kaira
authors: Kimihiro
authors: K
authors: Shimizu
authors: Shigebumi
authors: S
authors: Tanaka
authors: Tatsuo
authors: T
authors: Suga
authors: Takeshi
authors: T
authors: Hisada
authors: Tamotsu
authors: T
authors: Ishizuka
authors: Ryusei
authors: R
authors: Saito
authors: Kunio
authors: K
authors: Dobashi
authors: Masatomo
authors: M
authors: Mori
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib