title: Interleukin-2, interferon-alpha and interleukin-2 plus interferon-alpha in renal cell carcinoma. A randomized phase II trial.
abstract: BACKGROUND
  The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC).
  
  
  METHODS
  In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rlL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 10(6) lU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-alpha at a daily dose of 6 x 10(6) IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity.
  
  
  RESULTS
  Twenty-three percent (95% CI:+/-17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI:+/-11.9) and 9% (95% CI:+/-11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN.
  
  
  CONCLUSIONS
  Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.
authors.affiliation: Department of Medical Oncology II, National Institute for Cancer Research, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Boccardo
authors.forename: A
authors.initials: A
authors.lastname: Rubagotti
authors.forename: L
authors.initials: L
authors.lastname: Canobbio
authors.forename: E
authors.initials: E
authors.lastname: Galligioni
authors.forename: R
authors.initials: R
authors.lastname: Sorio
authors.forename: A
authors.initials: A
authors.lastname: Lucenti
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
authors.forename: E
authors.initials: E
authors.lastname: Ruggeri
authors.forename: G
authors.initials: G
authors.lastname: Landonio
authors.forename: C
authors.initials: C
authors.lastname: Baiocchi
authors.forename: C
authors.initials: C
authors.lastname: Besana
authors.forename: G
authors.initials: G
authors.lastname: Citterio
authors.forename: M
authors.initials: M
authors.lastname: De Rosa
authors.forename: F
authors.initials: F
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2