TY - JOUR
T1 - A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating factor administered by IV bolus or continuous infusion.
AU - Rifkin, R. M.
AU - Hersh, E. M.
AU - Salmon, S. E.
PY - 1988/8
Y1 - 1988/8
N2 - 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.
AB - 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.
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M3 - Article
C2 - 3071327
AN - SCOPUS:0024065254
SN - 0301-0457
SP - 125
EP - 133
JO - Behring Institute Mitteilungen
JF - Behring Institute Mitteilungen
IS - 83
ER -