title: Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial.
abstract: BACKGROUND
  Few randomized trials have compared the survival benefit of interferon-alfa over controls in metastatic renal cell carcinoma, and none has been performed using interleukin-2. The Programme Etude Rein Cytokines (PERCY) Quattro trial was designed to evaluate both cytokines for their survival benefit to intermediate prognosis patients, who represent the majority of candidates for these treatments.
  
  
  METHODS
  Patients were randomized in a 2-by-2 factorial design to medroxyprogesterone acetate 200 mg daily, interferon-alfa 9 million IU 3 times a week, subcutaneous interleukin-2 9 million IU daily, or a combination of both cytokines. Tumor response was evaluated at Week 12 and Month 6; progression-free patients received further identical treatment for a maximum of 3 additional months. Primary endpoint was overall survival; secondary endpoints were disease-free survival, response rate, toxicity, and quality of life. Survival was analyzed on an intent-to-treat basis.
  
  
  RESULTS
  From January 2000 to July 2004, 492 patients were enrolled. Analysis was performed after a 29.2-month median follow-up (range, 0 months to 54.6 months). There were no significant survival differences between the 244 interferon-alfa-treated patients and 248 noninterferon-alfa patients (hazard ratio, 1.00; 95% CI, 0.81-1.24) or between the 247 interleukin-2 and 245 noninterleukin-2-treated patients (hazard ratio, 1.07; 95% CI, 0.87-1.33; log rank, 0.99 and 0.52, respectively). Grade 3-4 toxicities were significantly more frequent in cytokine-treated patients than in medroxyprogesterone-treated patients.
  
  
  CONCLUSIONS
  Subcutaneous interleukin-2 and/or interferon-alfa provide no survival benefit in metastatic renal cancers of intermediate prognosis, and they induce a significant risk of toxicity. Newly available angiogenesis inhibitors should be preferred for these patients.
authors.affiliation: Université de Lyon, Department of Medical Oncology and Cytokines & Cancer Research Unit, Leon Berard Center, INSERM U590, Lyon, France. negrier@lyon.fnclcc.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.forename: David
authors.initials: D
authors.lastname: Perol
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.forename: Remy
authors.initials: R
authors.lastname: Delva
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sevin
authors.forename: Armelle
authors.initials: A
authors.lastname: Caty
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008525:Medroxyprogesterone / Q000008:administration & dosage*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011788:Quality of Life; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D008525:Medroxyprogesterone