Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis.
AuthorsPrendiville, Joseph A
Lind, Michael J
Ghosh, Anna K
Stern, Peter L
AffiliationCRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
MetadataShow full item record
Abstract19 patients with advanced cancer were entered into a phase I study of recombinant human interleukin-4 (rhu IL-4). The predominant clinical side-effects included flu-like symptoms, gastrointestinal upset, lethargy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occurred; this was life threatening in 1 patient. The maximum tolerated dose (MTD) was 400 micrograms/m2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes suggesting IL-4 induced liver damage. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) showed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.
CitationRecombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis. 1993, 29A (12):1700-7 Eur. J. Cancer
JournalEuropean Journal of Cancer
- A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia.
- Authors: Bernstein SH, Fay J, Frankel S, Christiansen N, Baer MR, Jacobs C, Blosch C, Hanna R, Herzig G
- Issue date: 1999
- Phase I evaluation of thrice-daily intravenous bolus interleukin-4 in patients with refractory malignancy.
- Authors: Atkins MB, Vachino G, Tilg HJ, Karp DD, Robert NJ, Kappler K, Mier JW
- Issue date: 1992 Nov
- A phase I study of recombinant human interleukin-4 administered by the intravenous and subcutaneous route in patients with advanced cancer: immunological studies.
- Authors: Ghosh AK, Smith NK, Prendiville J, Thatcher N, Crowther D, Stern PL
- Issue date: 1993 May-Jun
- A phase I and pharmacokinetic study of subcutaneously-administered recombinant human interleukin-4 (rhuIL-4) in patients with advanced cancer.
- Authors: Davis ID, Maher DW, Cebon JS, Green MD, Fox RM, McKendrick JJ, Rybak ME, Boyd AW
- Issue date: 2000
- Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies.
- Authors: Atkins MB, Robertson MJ, Gordon M, Lotze MT, DeCoste M, DuBois JS, Ritz J, Sandler AB, Edington HD, Garzone PD, Mier JW, Canning CM, Battiato L, Tahara H, Sherman ML
- Issue date: 1997 Mar