title: First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer: a phase II study.
abstract: OBJECTIVE
  We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) to assess its efficacy and toxicity.
  
  
  METHODS
  Patients received 250 mg doses of gefitinib daily. Administration of gefitinib was terminated if partial response (PR) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks. In these cases, platinum-based doublet chemotherapy was given as a salvage treatment. We evaluated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples.
  
  
  RESULTS
  Forty-two patients were enrolled between March and November 2003, with 40 of these patients being eligible. The response rate was 30% (95% CI, 17% to 47%). The most common toxicity included grade 1 or 2 acne-like rash (50%) and grade 1 diarrhea (18%). Grade 2 or 3 hepatic toxicity was observed in 8% of patients. Four patients developed grade 5 interstitial lung disease (ILD). Thirty patients received second-line chemotherapy. Median survival time was 13.9 months (95% CI, 9.1 to 18.7 months), and the 1-year survival rate was 55%. Tumor samples were available in 13 patients, including four cases of PR, six cases of stable disease, and three cases of progressive disease. EGFR mutations (deletions in exon 19 or point mutations [L858R or E746V]) were detected in four tumor tissues. All four patients with EGFR mutation achieved PR with gefitinib treatment.
  
  
  CONCLUSIONS
  Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. siniho@east.ncc.go.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Niho
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Yoh
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kakinuma
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishiwaki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013902:Radiography, Thoracic; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib