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 s ide-effects included flu-like symptoms, gastrointestinal upset, lethar gy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occu rred; this was life threatening in 1 patient. The maximum tolerated do se (MTD) was 400 mug/m2/day. Biochemical toxicity was limited to asymp tomatic elevation of liver enzymes suggesting IL-4 induced liver damag e. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) fr om a small compartment (mean Vd = 4.9 +/- 3.681) probably indicating t hat IL-4 is retained in the systemic circulation or at most the extrac ellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) show ed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.