title: Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m(2) days 1 and 8) and either cisplatin (75 mg/m(2) day 1) or carboplatin (5 x area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety.
  
  
  RESULTS
  The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC)-erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease.
  
  
  CONCLUSIONS
  Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.
authors.affiliation: Chinese University of Hong Kong, Sir YK Pau Cancer Center, Hong Kong.
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jorge
authors.initials: J
authors.lastname: Ignacio
authors.forename: Meilin
authors.initials: M
authors.lastname: Liao
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boyer
authors.forename: Marina
authors.initials: M
authors.lastname: Chua-Tan
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.forename: Aru W
authors.initials: AW
authors.lastname: Sudoyo
authors.forename: Kate
authors.initials: K
authors.lastname: Jin
authors.forename: Michael
authors.initials: M
authors.lastname: Johnston
authors.forename: Winsome
authors.initials: W
authors.lastname: Chui
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin; D000093542:Gemcitabine