Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulating factor.
To assess the toxicity, pharmacokinetics, and local and systemic effects of the intraperitoneal (i.p.) administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) at various dosages, 13 patients with predominantly i.p. malignancies refractory to standard chemotherapy were studied. GM-CSF was administered intravenously (i.v.) for 5 consecutive days; 21 days later the same dosage of GM-CSF was administered i.p. for 5 consecutive days. Four dosage levels were studied: 1, 2, 4, and 8 micrograms/kg/day. GM-CSF was well tolerated after i.v. and i.p. administration at doses up to 8 micrograms/kg/day. A transient fall followed by an elevation of circulating white cells was observed over a 24-h period after both i.v. and i.p. GM-CSF administration (mean minimum +/- SE as % baseline): 38 +/- 8% at 30 min after i.v. administration, 21 +/- 5% at 60 min after i.p. administration; mean maximum: 220 +/- 41% at 6 h after i.v. administration, 202 +/- 39% at 12 h after i.p. administration). The magnitude and time course of these changes were very similar for the two routes despite an up to 400-fold difference in serum GM-CSF levels at the same time points. Changes in leukocyte count and differential and neutrophil function were also similar over the 3-week period after both i.v. and i.p. administration. In the only patient who had i.p. GM-CSF levels assayed, i.p. administration achieved high levels of GM-CSF in peritoneal fluid (Cmax 343 ng/ml) with maintenance of high concentrations over 24 h (C24h 128 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Toner
G C
GC
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Gabrilove
J L
JL
Gordon
M
M
Crown
J
J
Jakubowski
A A
AA
Meisenberg
B
B
Sheridan
C
C
Boone
T
T
Vincent
M E
ME
Markman
M
M
D000328:Adult; D000368:Aged; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor