title: Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.
abstract: OBJECTIVE
  A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC).
  
  
  METHODS
  Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a 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), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed.
  
  
  RESULTS
  Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy.
  
  
  CONCLUSIONS
  Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.
authors.affiliation: Genitourinary Oncology Service, Division of Solid Tumor Oncology, and the Departments of Medical Imaging and Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: B A
authors.initials: BA
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Bacik
authors.forename: L H
authors.initials: LH
authors.lastname: Schwartz
authors.forename: D M
authors.initials: DM
authors.lastname: Nanus
authors.forename: T
authors.initials: T
authors.lastname: Mariani
authors.forename: P
authors.initials: P
authors.lastname: Loehrer
authors.forename: G
authors.initials: G
authors.lastname: Wilding
authors.forename: D L
authors.initials: DL
authors.lastname: Fairclough
authors.forename: D
authors.initials: D
authors.lastname: Cella
authors.forename: M
authors.initials: M
authors.lastname: Mazumdar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D015474:Isotretinoin / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D011788:Quality of Life; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin