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 …

J Prendiville, N Thatcher, M Lind, R McIntosh… - European Journal of …, 1993 - Elsevier
J Prendiville, N Thatcher, M Lind, R McIntosh, A Ghosh, P Stern, D Crowther
European Journal of Cancer, 1993Elsevier
Abstract 19 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 μg/m
2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes …
Abstract
Abstract 19 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 μg/m 2/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 T 1 2= 19±8.7 min) from a small compartment (mean V d= 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.
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