title: Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01.
abstract: OBJECTIVE
  This randomized, double-blind, placebo-controlled phase III study aimed to determine whether thalidomide prolongs survival of patients with extensive-disease small-cell lung cancer (SCLC).
  
  
  METHODS
  One hundred nineteen patients received two courses of etoposide, cisplatin, cyclophosphamide, and 4'-epidoxorubicin (PCDE). Responder patients who had recovered from chemotherapy toxicity were randomly assigned to receive four additional PCDE cycles plus thalidomide (400 mg daily) or placebo.
  
  
  RESULTS
  After the first two PCDE cycles, objective response rate was 81.5%, and 92 patients were randomly assigned to placebo (n = 43) or thalidomide (n = 49). Median exposure duration to placebo was 4.5 months, and median exposure to thalidomide was 4.9 months. Patients treated with thalidomide had a longer survival compared with patients who received placebo, although the difference was not statistically significant (minimal follow-up, 3 years; median survival time, 11.7 v 8.7 months, respectively; log-rank test: hazard ratio [HR] = 0.74; 95% CI, 0.49 to 1.12; P = .16). Patients with a performance status (PS) of 1 or 2 who received thalidomide had a significantly longer survival (HR = 0.59; 95% CI, 0.37 to 0.92; P = .02). The disease also progressed slower in patients with PS of 1 or 2 receiving thalidomide (HR = 0.54; 95% CI, 0.36 to 0.87; P = .02), whereas the difference did not reach statistical significance for the whole population (HR = 0.74; 95% CI, 0.49 to 1.12; P = .15). Neuropathy occurred more frequently in the thalidomide group compared with the placebo group (33% v 12%, respectively).
  
  
  CONCLUSIONS
  Treatment with thalidomide was not associated with a significant improvement in survival of SCLC patients. There was pronounced heterogeneity in survival outcomes between groups of patients. Some benefit was observed among patients with a PS of 1 or 2 (exploratory analyses), deserving further studies targeting angiogenesis in this disease.
authors.affiliation: Centre Hospitalier Universitaire, Montpellier Cedex 5, France. jl-pujol@chu-montpellier.fr
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Breton
authors.forename: Radj
authors.initials: R
authors.lastname: Gervais
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Tanguy
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Philippe
authors.initials: P
authors.lastname: David
authors.forename: Henri
authors.initials: H
authors.lastname: Janicot
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.forename: Sabine
authors.initials: S
authors.lastname: Gameroff
authors.forename: Jean
authors.initials: J
authors.lastname: Genève
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
mesh_terms: D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*
chemical_list: D013792:Thalidomide