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

To assess any synergistic stimulatory effect in vivo of Interleukin 3 (IL-3) and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) u pon white cell and platelet counts, toxicity and anti-tumour effect, w e conducted this phase I study. IL-3 0.25, 0.5 or 5 mu g/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 receive d sequential or overlapping treatment with continuous i.v. infusion of GM-CSF 1 or 3 mu g/kg/day for up to 10 days. Monotherapy with IL-3 pr oducted significant dose related increases in platelets and white cell . counts. Combinations of IL-3 and GM-CSF also produced increases in w hite cell counts, but these were no greater than would be expected fol lowing GM-CSF treatment alone. There was a trend for platelets to incr ease more in patients receiving IL-3 and GM-CSF than those receiving I L-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 r eached and antitumour effects were not seen. Future studies using comb inations of IL-3 5 mu g/kg/day and GM-CSF 3 mu g/kg/day may help to de fine the optimal therapeutic regimen. Copyright (C) 1996 Elsevier Scie nce Ltd