title: Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2: prognostic factors and treatment selection based on two large randomized clinical trials.
abstract: OBJECTIVE
  Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2.
  
  
  METHODS
  Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy.
  
  
  RESULTS
  Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival times were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase >or=200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy.
  
  
  CONCLUSIONS
  Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy.
authors.affiliation: Mount Sinai Cancer Center, Miami Beach, Florida 33140, USA. rlilenba@msmc.com
authors.forename: Rogerio
authors.initials: R
authors.lastname: Lilenbaum
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Villaflor
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
authors.forename: Kenneth
authors.initials: K
authors.lastname: O'Byrne
authors.forename: Mary
authors.initials: M
authors.lastname: O'Brien
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
authors.forename: Mark
authors.initials: M
authors.lastname: Socinski
authors.forename: Fred B
authors.initials: FB
authors.lastname: Oldham
authors.forename: Larissa
authors.initials: L
authors.lastname: Sandilac
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D015415:Biomarkers; D003841:Deoxycytidine; D014747:Vinblastine; D016190:Carboplatin; D017239:Paclitaxel; D000077235:Vinorelbine; D000093542:Gemcitabine