Background: A phase I study using recombinant human interleukin-4 (rhuIL-4) administered as a continuous intravenous infusion was conducted in patients with advanced cancer to study the toxicity profile and to determine the maximum tolerated dose (MTD) of this cytokine.
Methods: Twenty-six patients with non-hematologic malignancies were treated with escalating doses of rhuIL-4 administered as 24-hour continuous intravenous infusion on days 1-5 and 15-19 every 28 days. The dose levels of rhuIL-4 were: dose level I-0.25 microg/kg/day (3 patients), dose level II-0.5 microg/kg/day (5 patients), dose level III-1.0 microg/kg/day (3 patients), dose level IV-2.0 microg/kg/day (10 patients) and dose level V-4.0 microg/kg/day (5 patients).
Results: Dose limiting toxicity of continuous infusion rhuIL-4 occurred at 4.0 microg/kg/day D1-5 and 15-19, in three of five patients and consisted of hematologic (thrombocytopenia and prolongation of PT) and neurologic (headache and neurocortical toxicity) toxicity. A mild flu-like syndrome characterized by fever, chills, fatigue, headache, anorexia, arthralgias and myalgias was seen almost universally, occurred more commonly and with increasing severity with higher dose levels and resolved completely on discontinuing therapy with rhuIL-4. None of the enrolled patients had an objective response to treatment with continuous infusion rhuIL-4.
Conclusions: A five-day continuous infusion of rhuIL-4 given biweekly is well tolerated with a MTD of 2.0 microg/kg/day.