title: Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America.
abstract: BACKGROUND
  To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and 1992.
  
  
  METHODS
  Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time.
  
  
  RESULTS
  Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of this time period (1972-1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001).
  
  
  CONCLUSIONS
  Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival.
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Boris
authors.initials: B
authors.lastname: Freidlin
authors.forename: Scott
authors.initials: S
authors.lastname: Saxman
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012106:Research / Q000639:trends; D012189:Retrospective Studies; D018426:SEER Program; D016019:Survival Analysis