A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating factor administered by IV bolus or continuous infusion.
Sixteen patients with primary or secondary bone marrow failure were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) given as either an intravenous bolus or by continuous infusion. The dose range studied was from 15 micrograms/m2/d to 960 micrograms/m2/d. Administration of rGM-CSF on a bolus schedule failed to elicit a hematologic response, but resulted in side effects of epigastric distress and eructation in over 30% of administered courses. Administration of rGM-CSF by continuous infusion resulted in a dose-dependent increase in the total leukocyte, granulocyte, and eosinophil counts. The mean maximal rise in granulocyte count was 8.5-fold. After cessation of therapy, blood counts returned to near baseline in most patients by 7 days. A 36 percent decrease from baseline in mean serum cholesterol level was observed in the continuous infusion group, but not in patients receiving rGM-CSF as an IV bolus. Fever, fatigue, and bone pain were dose-limiting in the continuous infusion group at a dose of 240 micrograms/m2/d. The maximally tolerated dose was 480 micrograms/m2/d. No life-threatening toxicities were observed in either group. Our data demonstrate that continuous infusion rGM-CSF is biologically active and non-toxic at a dose of 120 micrograms/m2/d in patients with bone marrow failure.
Rifkin
R M
RM
Department of Internal Medicine, University of Arizona College of Medicine, Tucson 85724.
Hersh
E M
EM
Salmon
S E
SE
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000741:Anemia, Aplastic / Q000188:drug therapy; D001853:Bone Marrow / Q000473:pathology; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004341:Drug Evaluation; D005258:Felty Syndrome / Q000188:drug therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor