title: First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung.
abstract: OBJECTIVE
  Gefitinib has shown high response rate and improved progression-free survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy.
  
  
  METHODS
  In this randomized phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ function were randomly assigned to receive either gefitinib (250 mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m(2) on days 1 and 8; cisplatin 80 mg/m(2) on day 1 every 3 weeks, for up to nine courses). The primary objective was to demonstrate better overall survival (OS) for gefitinib compared with GP in chemotherapy-naive NSLAs.
  
  
  RESULTS
  Three hundred nine patients were analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to 1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to 1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101). Myelosuppression, renal insufficiency, and fatigue were more common in the GP arm, but skin toxicities and liver dysfunction were more common in the gefitinib arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease and died.
  
  
  CONCLUSIONS
  Gefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.
authors.affiliation: National Cancer Center, Goyang, Republic of Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Myung Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.forename: Jung-Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Han
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sook Jung
authors.initials: SJ
authors.lastname: Jo
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; D002945:Cisplatin; D000077156:Gefitinib; D000093542:Gemcitabine