Details

Autor(en) / Beteiligte

• THOMPSON, J. A
• LEE, D. J
• WELBY COX, W
• LINDGREN, C. G
• COLLINS, C
• NERAAS, K. A
• DENNIN, R. A
• FEFER, A

Titel

Recombinant interleukin 2 toxicity, pharmacokinetics, and immunomodulatory effects in a phase I trial

Ist Teil von

• Cancer research (Chicago, Ill.), 1987-08, Vol.47 (15), p.4202-4207

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

1987

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Twenty-two patients with refractory malignancies were treated with four escalating weekly doses of recombinant interleukin 2 (IL2), given either i.v. by 2- or 24-h infusion, or s.c. A 1-wk washout period between each dose of IL2 was provided for the evaluation for pharmacokinetic and immunomodulatory effects. The maximum i.v. dose was 30 X 10(6) units; the dose-limiting toxicities were fever, flu-like symptoms, and hypotension. The maximum s.c. dose was 3 X 10(6) because of volume limitations with s.c. injection. No tumor regression was seen. During infusions of 3 X 10(6) units over 2 h or 24 h, serum IL2 levels greater than or equal to 223 units/ml or 16 units/ml were maintained, respectively; with s.c. injection of 3 X 10(6) units, levels greater than 20 units/ml were maintained for 9 h. Marked lymphopenia was observed 24 h after the initiation of IL2 doses which was completely reversible when measured prior to the next dose. The lymphopenia was nonselective; T- and B-lymphocytes decreased in an IL2 dose-dependent manner, without consistent change in the OKT4:OKT8 ratio. No change was detected in monocyte expression of HLA-Dr or T-cell expression of the IL2 receptor. The in vitro generation of lymphokine-activated killer cytotoxicity decreased sharply and transiently shortly after i.v. doses. Mitogen responsiveness, delayed-type hypersensitivity, natural killer cytotoxicity, and mixed-lymphocyte reactivity were unchanged or decreased transiently shortly after IL2 doses. These studies help define the bioavailability of IL2 by i.v. or s.c. routes, and they will aid in the design of studies utilizing daily doses of IL2.