title: Phase 2 trial of pemetrexed disodium and carboplatin in previously untreated extensive-stage small cell lung cancer, N0423.
abstract: BACKGROUND
  In extensive-stage small cell lung cancer (SCLC), the combination of pemetrexed plus carboplatin has shown activity and appeared to be well-tolerated. We conducted a trial to confirm the efficacy and to assess the tolerability of this chemotherapy combination.
  
  
  METHODS
  Patients with untreated extensive-stage SCLC were enrolled in this phase 2 open-labeled study. They receive pemetrexed 500 mg/m(2) and carboplatin (area under the curve of 5) every 21 days for a maximum 6 cycles. The primary endpoint for this trial was the confirmed response rate and the accrual goal was 70 patients.
  
  
  RESULTS
  Forty-six eligible patients (29 aged <70 years, 17 aged >or=70 years) were accrued to this study. The efficacy outcomes were similar between the 2 age groups. Overall, the confirmed response rate was 35% (16 of 46; 95% confidence interval [CI], 21%-50%), where all 16 were partial responses. On the basis of these results, we had strong evidence that the study would not meet the preset efficacy criteria and was, therefore, closed before full accrual. The median duration of response was 4.4 months (95% CI, 2.9-5.2). Median overall survival for patients aged <70 years and aged >or=70 years was 9.2 months (95% CI, 5.4-11.6) and 10.8 months (95% CI, 2.2-14.3), respectively. Grade 3 or higher toxicity rates were similar between the younger and older patients. Grade 3/4 and grade 4 hematological toxicities were observed in 46% and 26% of patients, respectively.
  
  
  CONCLUSIONS
  Although well-tolerated, the combination of pemetrexed and carboplatin is not as effective as standard therapy in patients with untreated extensive-stage SCLC.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Cheng E
authors.initials: CE
authors.lastname: Chee
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
authors.forename: Albert M
authors.initials: AM
authors.lastname: Bernath
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.forename: Garth D
authors.initials: GD
authors.lastname: Nelson
authors.forename: Julian
authors.initials: J
authors.lastname: Molina
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Preston D
authors.initials: PD
authors.lastname: Steen
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin