title: A randomised dose escalation study of subcutaneous interleukin 2 with and without levamisole in patients with metastatic renal cell carcinoma or malignant melanoma.
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.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, London, UK.
authors.forename: F Y
authors.initials: FY
authors.lastname: Ahmed
authors.forename: G A
authors.initials: GA
authors.lastname: Leonard
authors.forename: R
authors.initials: R
authors.lastname: A'Hern
authors.forename: A E
authors.initials: AE
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Lorentzos
authors.forename: H
authors.initials: H
authors.lastname: Atkinson
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: M C
authors.initials: MC
authors.lastname: Nicolson
authors.forename: P G
authors.initials: PG
authors.lastname: Riches
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D007958:Leukocyte Count / Q000187:drug effects; D007978:Levamisole / Q000008:administration & dosage* / Q000009:adverse effects; D008214:Lymphocytes / Q000187:drug effects; D008545:Melanoma / Q000276:immunology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D007978:Levamisole