title: Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839, "Iressa") on an expanded access study.
abstract: OBJECTIVE
  To investigate the anti-tumor activity and toxicity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839 or Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE), in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  This was an open label, expanded access program (EAP) of oral gefitinib administered at 250 mg per day continuously until evidence of undue toxicity or disease progression.
  
  
  RESULTS
  Two hundred consecutive patients with advanced NSCLC were enrolled in this study. The median number of prior chemotherapy regimens was 2 (range 0-6). One hundred seventy-two patients were treated with gefitinib; 23 expired from disease progression prior to treatment and 5 withdrew their consent. One hundred fifty-four patients are evaluable for toxicity; 8 (5.2%) experienced grade 3/4 toxicity; 2 patients discontinued therapy for grade 3 rash and one for grade 3 nausea. Of 172 patients evaluable for efficacy, 7 (4.1%; 95% CI; 1.7-8.2%) experienced a partial response (PR); 60 patients (34.9%) had stable disease (SD) as their best response. Median survival for all patients was 4.5 months (95% CI; 4.1-4.9 months). One-year survival was 29%. Significant independent prognostic factors associated with improved survival were female gender, good performance status (0/1), and adenocarcinoma histology.
  
  
  CONCLUSIONS
  Gefitinib has anti-tumor activity, in a heterogeneous population of NSCLC patients treated on the EAP study. Treatment with gefitinib in this population is associated with a longer survival in women, those with good performance status and in patients with adenocarcinomas. These findings need to be further validated in additional clinical studies.
authors.affiliation: Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, 44 Binney Street, D1234, Boston, MA 02115, USA. pjanne@partners.org
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Sarada
authors.initials: S
authors.lastname: Gurubhagavatula
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: Joan
authors.initials: J
authors.lastname: Lucca
authors.forename: Patricia
authors.initials: P
authors.lastname: Ostler
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Skarin
authors.forename: Panos
authors.initials: P
authors.lastname: Fidias
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006304:Health Status; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib