title: Randomized phase II/III trial of interferon Alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell Carcinoma: the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951).
abstract: OBJECTIVE
  A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.
  
  
  METHODS
  Three hundred twenty patients were randomly assigned to treatment with IFN-alpha-2a plus 13-CRA or to IFN-alpha-2a alone. IFN-alpha-2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU by increments of 3 MU. Patients randomly assigned to combination therapy received oral 13-CRA 1 mg/kg/d plus IFN-alpha-2a.
  
  
  RESULTS
  Median time to progression was 5.1 months for patients treated with the combination and 3.4 months for patients on IFN-alpha-2a alone (P = .008). Progression-free survival rates at 6 months were 43% for patients receiving combined therapy and 30% for patients on IFN-alpha-2a, and at 12 months, 27% and 17%, respectively. Median overall survival was 17.3 months for patients on IFN-alpha-2a and 13-CRA, and 13.2 months for patients treated with IFN-alpha-2a (P = .048). Twenty-two percent of the patients receiving the combination stopped treatment due to toxicity, as compared with 16% on IFN-alpha-2a.
  
  
  CONCLUSIONS
  Progression-free and overall survival for patients with progressive metastatic renal cell carcinoma treated with IFN-alpha-2a plus 13-CRA were significantly longer compared with patients on IFN-alpha-2a alone (P = .007 and P = .048, respectively). Improvement in efficacy in the combination arm was accompanied by increased, though not serious, toxicity.
authors.affiliation: Department of Clinical Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway. ninaaass@radium.uio.no
authors.forename: Nina
authors.initials: N
authors.lastname: Aass
authors.forename: Pieter H M
authors.initials: PH
authors.lastname: De Mulder
authors.forename: Gerald H J
authors.initials: GH
authors.lastname: Mickisch
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.forename: Allan T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: Hein
authors.initials: H
authors.lastname: van Poppel
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fossa
authors.forename: Linda
authors.initials: L
authors.lastname: de Prijck
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sylvester
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D015474:Isotretinoin / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin