Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma

J Interferon Cytokine Res. 2001 Apr;21(4):257-63. doi: 10.1089/107999001750169934.


Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Ascites / etiology
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy*
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use*
  • Interleukin-12 / administration & dosage*
  • Interleukin-12 / adverse effects
  • Interleukin-12 / pharmacokinetics
  • Interleukin-12 / therapeutic use*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neutropenia / etiology
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Stomatitis / etiology


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Interleukin-12