The clinical experience with interleukin-2 in cancer therapy.
In May 1992, interleukin-2 (IL-2) was formally approved by the U.S. Food and Drug Administration for use in cancer treatment based on its activity in metastatic renal cell carcinoma. IL-2 alone or in combination with activated lymphocytes or other cytokines has significant anti-tumor activity against renal cell carcinoma and melanoma with response rates of 15-20%, some of which are quite durable. Limited anti-tumor effects have been noted in some patients with colorectal cancer and lymphoma. Too few patients have been studied to establish the level of activity in most other specific tumor types. The mechanism of this anti-tumor effect appears to be entirely mediated by the immunostimulatory effects of IL-2. Toxicities are dose related, but are substantial and similar regardless of the schedule of administration. Randomized trials have failed to establish (1) the superiority of high-dose bolus over continuous infusion IL-2, (2) the superiority of IL-2 plus interferon over IL-2 alone, or (3) the superiority of IL-2 plus LAK cells versus IL-2 alone. Further investigation is needed to determine the optimum dose and schedule from the standpoint of cost:benefit and risk:benefit, and to determine the role of IL-2 in the therapy of other malignant diseases.
Dillman
R O
RO
Patty and George Hoag Cancer Center, Newport Beach, California 92663.
D002292:Carcinoma, Renal Cell / Q000628:therapy; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D017277:Drug Approval / Q000191:economics; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000737:chemistry / Q000191:economics / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy; D008545:Melanoma / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D007155:Immunologic Factors; D007376:Interleukin-2