title: Gefitinib (ZD1839): therapy in selected patients with non-small cell lung cancer (NSCLC)?
abstract: OBJECTIVE
  To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP).
  
  
  METHODS
  A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed.
  
  
  RESULTS
  In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers.
  
  
  CONCLUSIONS
  In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.
authors.affiliation: Medical Oncology, Centro Oncologico Ematologico Subalpino (C.O.E.S.), Azienda Ospedaliera S. Giovanni Battista, Turin, Italy. diego.dongiovanni@libero.it
authors.forename: Diego
authors.initials: D
authors.lastname: Dongiovanni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Daniele
authors.forename: Carla
authors.initials: C
authors.lastname: Barone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dongiovanni
authors.forename: Camilla
authors.initials: C
authors.lastname: Fissore
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.forename: Luigia
authors.initials: L
authors.lastname: Macrì
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussolati
authors.forename: Lucio
authors.initials: L
authors.lastname: Buffoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Raffaella
authors.initials: R
authors.lastname: Grillo
authors.forename: Nadia
authors.initials: N
authors.lastname: Birocco
authors.forename: Alfredo
authors.initials: A
authors.lastname: Addeo
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Marina
authors.initials: M
authors.lastname: Schena
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; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib