Cytokine combinations: therapeutic use in patients with advanced renal cell carcinoma

Semin Oncol. 2000 Apr;27(2):204-12.


Treatment of metastatic renal cell carcinoma (RCC) remains unsatisfactory. To enhance the antitumor effects of various cytokines, combinations of these agents have been investigated. Interleukin-2 (IL-2) and interferon-alfa (IFN-alpha) have been combined based on data from preclinical studies suggesting synergism. A review of available phase I and II trials in more than 1,400 patients indicates that response rates are approximately 20%. Complete regressions are seen in 3% to 5% of patients. To demonstrate that this combination increases overall response rates, randomized trials were required. The results of a phase III study demonstrate a significantly improved response rate (18.6%) and 1-year event-free survival (20.9%) for patients treated with continuous infusion recombinant (r) IL-2 and subcutaneous IFN-alpha compared with either cytokine alone. The toxicity of rlL-2 and IFN-alpha is related to cytokine dose and schedule, but appears less than that reported with high-dose rIL-2. Analysis of prognostic factors and surrogate marker changes have been conducted. Performance status and number of disease sites predict response. rIL-2 and IFNalpha were then combined with fluorouracil, with initial reports suggesting response rates greater than 40%. Recent reports indicate 1% to 39% of patients responding. In a group of 836 patients with metastatic RCC receiving this therapy, 25.3% responded. Randomized trials comparing chemoimmunotherapy to rIL-2 and/or IFN-alpha are now required. The biologic basis and rationale for utilization of cytokines are strong. Clinical results are consistent with improved response rates in patients receiving rIL-2 and IFN-alpha. Continued investigation of novel and new treatment approaches remains a priority.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / therapy*
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Fluorouracil / administration & dosage
  • Humans
  • Interferon-beta / administration & dosage
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / therapy*
  • Lymphocyte Subsets / drug effects
  • Neoplasm Metastasis
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / administration & dosage
  • Remission Induction
  • Tumor Necrosis Factor-alpha / administration & dosage


  • Adjuvants, Immunologic
  • Interleukin-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-beta
  • Fluorouracil