Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

Br J Cancer. 2006 Nov 6;95(9):1167-73. doi: 10.1038/sj.bjc.6603391. Epub 2006 Oct 10.


We conducted a non-randomised controlled phase II trial to investigate the role of preoperative administration of interleukin-2 (IL-2) in patients with renal cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients were allocated alternately to the two study groups: perioperative immunomodulation with IL-2 (IL-2 group; n=60) and perioperative immunomonitoring without immunomodulation (control group; n=60). Patients from the IL-2 group received four doses of 10 x 10(6) IU m(-2) twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 x 10(6) IU m(-2) subcutaneously until a day before the operation. Parameters of cellular and humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34, as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist, transforming growth factor-beta1, and vascular endothelial growth factor) were measured in peripheral venous blood at various intervals. Interleukin-2-related toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period, T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and IL-10 increased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Median follow-up was 40 months. Tumour-specific survival in the IL-2 group and the control group was 98 vs 81% after 1 year and 86 vs 73% after 5 years (P=0.04). A similar effect was found for progression-free survival. We conclude that IL-2 can be safely administered in the perioperative period and modulates immunological parameters. However, to validate the survival data, a larger randomised phase III trial is needed.

Publication types

  • Clinical Trial, Phase II
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Combined Modality Therapy
  • Constipation / chemically induced
  • Cytokines / analysis
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Injections, Subcutaneous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Leukocyte Count
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Treatment Outcome


  • Antigens, CD
  • Cytokines
  • Immunologic Factors
  • Interleukin-2