title: Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2.
abstract: OBJECTIVE
  A multicenter randomized phase II trial to evaluate two treatment strategies in the first-line management of advanced non-small-cell lung cancer (NSCLC) patients with a performance status (PS) of 2.
  
  
  METHODS
  Patients were assigned to erlotinib 150 mg orally daily until progression or to carboplatin (area under the curve [AUC] 6) and paclitaxel (200 mg/m(2) day 1 every 3 weeks) for up to four cycles. Patients who experienced progression or did not tolerate or refused further chemotherapy were allowed to cross over to erlotinib. The primary end point was progression-free survival (PFS). Secondary end points were response, survival, quality of life (QOL), and a retrospective molecular correlation.
  
  
  RESULTS
  Fifty-two patients were randomly assigned to erlotinib and 51 to chemotherapy. Partial responses were 2% and 12%, respectively. Median PFS was 1.9 months in the erlotinib arm and 3.5 months in the chemotherapy arm (hazard ratio [HR] = 1.45; 95% CI, 0.98 to 2.15; P = .06). Median survival times were 6.5 and 9.7 months, respectively (HR = 1.73; 95% CI, 1.09 to 2.73; P = .018). Patients who crossed over to erlotinib had a median survival of 14.9 months. Sex, histology, skin rash, and smoking history predicted outcome with erlotinib. Rash and diarrhea were more common with erlotinib; emesis, alopecia, peripheral neuropathy, and fatigue were more common with chemotherapy. QOL was similar between the two arms. Molecular correlation was limited by available samples.
  
  
  CONCLUSIONS
  Unselected patients with advanced NSCLC and PS 2 are best treated with combination chemotherapy as first-line therapy. Erlotinib may be considered in patients selected by clinical or molecular markers.
authors.affiliation: Mount Sinai Cancer Center; 4306 Alton Road; Miami Beach, FL 33140, USA. rlilenbaum@aptiumoncology.com
authors.forename: Rogerio
authors.initials: R
authors.lastname: Lilenbaum
authors.forename: Rita
authors.initials: R
authors.lastname: Axelrod
authors.forename: Sachdev
authors.initials: S
authors.lastname: Thomas
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Leonard
authors.initials: L
authors.lastname: Seigel
authors.forename: Donald
authors.initials: D
authors.lastname: Albert
authors.forename: Karsten
authors.initials: K
authors.lastname: Witt
authors.forename: David
authors.initials: D
authors.lastname: Botkin
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage; 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*; D011795:Surveys and Questionnaires
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D017239:Paclitaxel