title: Rational selection of a control arm for randomised trials in metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Immunotherapy, and only immunotherapy, has reproducible, albeit limited efficacy in metastatic renal cell cancer (MRCC). Further improvement is warranted and progress will have to be investigated in randomised clinical trials, because the variable natural history of this disease precludes firm conclusions outside the context of controlled clinical studies. Currently, there is no general accepted standard arm to compare for those randomised clinical protocols. This needs to be established, which is the goal of this project.
  
  
  METHODS
  Interferon-alpha (IFN-alpha) or interleukin-2 (Il-2) are registered for the use in MRCC. Taking this regulatory affair into consideration, a systematic literature research using Medline Sources was carried out to identify large controlled clinical studies in MRCC, in which one or both of the registered drugs were involved. Scientific value of the trials was weighed, and the applicability, efficacy, and safety of the control arm was analysed.
  
  
  RESULTS
  13 large controlled studies qualified for this purpose, and a total of 3065 patients were included. IFN-alpha monotherapy, the combination of IFN-alpha and Il-2, and the combination of IFN-alpha, Il-2 and 5-fluorouracil (5-FU) were used as a standard treatment in decreasing frequency, respectively. There is no valid scientific proof that a combination of immunotherapies prolongs survival over monotherapies, but the combination of surgery and immunotherapy leads to a clear survival benefit over immunotherapy alone. IFN-alpha monotherapy has considerable less side effects than Il-2 based regimens.
  
  
  CONCLUSIONS
  An appealing safety profile, the applicability in an outpatient regimen, the possibility of less stringent selection criteria, and the proven life prolonging effect will make adjuvant monotherapy, in particular IFN-alpha monotherapy, after a tumournephrectomy currently the control-arm of choice in randomised trials for MRCC.
authors.affiliation: European Society of Oncologic Urology, Center of Operative Urology Bremen, Robert-Koch-Str 34a, D-28277 Bremen, Germany. gerald.mickisch@coub.de
authors.forename: G H J
authors.initials: GH
authors.lastname: Mickisch
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D009362:Neoplasm Metastasis; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design / Q000592:standards
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2