title: Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2.
abstract: OBJECTIVE
  To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2.
  
  
  METHODS
  In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m(2)) or CP (area under the curve of 5 and 500 mg/m(2), respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS).
  
  
  RESULTS
  A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm.
  
  
  CONCLUSIONS
  Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.
authors.affiliation: Instituto Nacional do Cancer, Rio deJaneiro.
authors.forename: Mauro
authors.initials: M
authors.lastname: Zukin
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Barrios
authors.forename: Jose Rodrigues
authors.initials: JR
authors.lastname: Pereira
authors.forename: Ronaldo De Albuquerque
authors.initials: Rde A
authors.lastname: Ribeiro
authors.forename: Carlos Augusto de Mendonça
authors.initials: CA
authors.lastname: Beato
authors.forename: Yeni Neron
authors.initials: YN
authors.lastname: do Nascimento
authors.forename: Andre
authors.initials: A
authors.lastname: Murad
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Franke
authors.forename: Maristela
authors.initials: M
authors.lastname: Precivale
authors.forename: Luiz Henrique de Lima
authors.initials: LH
authors.lastname: Araujo
authors.forename: Clarissa Serodio Da Rocha
authors.initials: CS
authors.lastname: Baldotto
authors.forename: Fernando Meton
authors.initials: FM
authors.lastname: Vieira
authors.forename: Isabele A
authors.initials: IA
authors.lastname: Small
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Ferreira
authors.forename: Rogerio C
authors.initials: RC
authors.lastname: Lilenbaum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin