title: Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.
abstract: BACKGROUND
  Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC) enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials.
  
  
  RESULTS
  We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis.
  
  
  RESULTS
  In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS) increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE) regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome.
  
  
  CONCLUSIONS
  The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ochi
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin