title: Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer.
abstract: OBJECTIVE
  Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC).
  
  
  METHODS
  Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m(2) on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m(2) on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin.
  
  
  RESULTS
  Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm.
  
  
  CONCLUSIONS
  Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. socinski@med.unc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Kartik
authors.initials: K
authors.lastname: Konduri
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczesna
authors.forename: Johnetta
authors.initials: J
authors.lastname: Blakely
authors.forename: Piotr
authors.initials: P
authors.lastname: Serwatowski
authors.forename: Nina A
authors.initials: NA
authors.lastname: Karaseva
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Mircea
authors.initials: M
authors.lastname: Dediu
authors.forename: Shengyan
authors.initials: S
authors.lastname: Hong
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.forename: Axel-Rainer
authors.initials: AR
authors.lastname: Hanauske
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: Susan C
authors.initials: SC
authors.lastname: Guba
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D005047:Etoposide; D016190:Carboplatin