A randomised dose escalation study of subcutaneous interleukin 2 with and without levamisole in patients with metastatic renal cell carcinoma or malignant melanoma

Br J Cancer. 1996 Oct;74(7):1109-13. doi: 10.1038/bjc.1996.498.

Abstract

We have examined the efficacy, toxicity and host immunological response of two different dose schedules of interleukin 2 (IL-2) given subcutaneously, daily for 3 months in patients with renal cell carcinoma (RCC) or metastatic melanoma (MM). We also examined the effect of adding the immune modulator levamisole to the two different schedules of IL-2. Thirty-nine patients were entered into two sequential phase I/II studies. Eighteen patients entered study 1 and were randomised to receive IL-2, 3 x 10(6) IU m-2 day-1, subcutaneously for 3 months with or without levamisole 50 mg t.d.s. p.o. on days 1-3 on alternate weeks. Twenty-one patients entered study 2 and were randomised to receive 5.4 x 10(6) IU m-2 day-1 subcutaneously for 3 months with or without levamisole 50 mg t.d.s. p.o. on days 1-3 on alternate weeks. Blood was taken for peripheral blood lymphocyte (PBL) phenotype analysis, and measurement of IL-2, soluble IL-2 receptor (sIL-2R) and neopterin concentration. Two patients with metastatic melanoma, one in each study, responded (11.8%); both received IL-2 alone. Observations of immunological parameters showed that treatment with subcutaneous IL-2 resulted in a significant rise in the percentage of PBLs bearing CD25, CD3/HLA-DR, CD56 and levels of IL-2 receptor and neopterin. The total white blood cell count (WBC) and total lymphocyte count rose significantly on day 18 compared with pretreatment levels. The addition of levamisole to either IL-2 schedule resulted in no significant changes in any immunological parameters. This study illustrates that prolonged subcutaneous IL-2 can be given safely in the outpatient setting. There was no evidence that levamisole acts as an immunomodulator in this study.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Adult
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy*
  • Humans
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy*
  • Leukocyte Count / drug effects
  • Levamisole / administration & dosage*
  • Levamisole / adverse effects
  • Lymphocytes / drug effects
  • Melanoma / immunology
  • Melanoma / therapy*

Substances

  • Adjuvants, Immunologic
  • Interleukin-2
  • Levamisole