An open phase I study to assess the biological effects of a continuous intravenous infusion of interleukin-3 followed by granulocyte macrophage-colony stimulating factor

Abstract

To assess any synergistic stimulatory effect in vivo of Interleukin 3 (IL-3) and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) upon white cell and platelet counts, toxicity and antitumour effect, we conducted this phase I study. IL-3 0.25, 0.5 or 5 μg/kg/day for 1, 4 or 7 days was given by continuous intravenous (i.V.) infusion to 35 patients with advanced malignancy. 21 of the 35 patients also received sequential or overlapping treatment with continuous i.v. infusion of GM-CSF 1 or 3 μg/kg/day for up to 10 days. Monotherapy with IL-3 producted significant dose related increases in platelets and white cell counts. Combinations of IL-3 and GM-CSF also produced increases in white cell counts, but these were no greater than would be expected following GM-CSF treatment alone. There was a trend for platelets to increase more in patients receiving IL-3 and GM-CSF than those receiving IL-3 alone, but this did not reach statistical significance. In general, IL-3 and combinations of IL-3 and GM-CSF were well tolerated and the most common side-effect was fever. A maximum tolerated dose was not reached and antitumour effects were not seen. Future studies using combinations of IL-3 5 μg/kg/day and GM-CSF 3 μg/kg/day may help to define the optimal therapeutic regimen.