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.
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 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.
Prendiville
J
J
CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
Thatcher
N
N
Lind
M
M
McIntosh
R
R
Ghosh
A
A
Stern
P
P
Crowther
D
D
D000328:Adult; D001682:Biological Availability; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D009369:Neoplasms / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012894:Sleep Stages; D013997:Time Factors
D011994:Recombinant Proteins; D015847:Interleukin-4