Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulting factor Journal Article


Authors: Toner, G. C.; Gabrilove, J. L.; Gordon, M.; Crown, J.; Jakubowski, A. A.; Meisenberg, B.; Sheridan, C.; Boone, T.; Vincent, M. E.; Markman, M.
Article Title: Phase I trial of intravenous and intraperitoneal administration of granulocyte-macrophage colony-stimulting factor
Abstract: Summary: To assess the toxicity, pharmacokinetics, and local and systemic effects of the intraperitoneal (i.p.) administraion of granulocyte-macrophage colony-stimulating factor (GM-CSF) at various dosages, 13 patinets 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 consecutive days. Four dosage levels were studied: 1, 2, 4, and 8 μg/kg/day. GM-CSF was well tolerated after i.v. and i.p. administration at doses up to 8 μ/kg/day. A transient fall followed by an elevation of circulation 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 ± 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 levels of GM-CSf in peritoneal fluid (Cmax343 ng/ml) with maintenance of high concerntrations over 24 h (C24h128 ng/ml). In a second patient who had i.p. fulid accessible, a dramatic increase (∼100-fold) in the number of neutophils in peritoneal fluid was observed after i.p. GM-CSF. Thus, GM-CSF can be administered safely into the peritoneal cavity. Intraperitoneal administration has similar slystemic effects to i.v. administration but may have additional local effects, such as attraction into the peritoneal cavity and activation of neutophils. Further exploration of i.p. GM-CSF in the mangement of intraperitoneal infection and malignancy is warranted. © 1994 Raven Press, Ltd., New York.
Keywords: adult; aged; clinical trial; neoplasms; cancer immunotherapy; leukopenia; inflammation; bone pain; chill; dyspnea; fever; cytokine; immunotherapy; thrombosis; ovary tumor; recombinant proteins; phase 1 clinical trial; infusions, intravenous; leukocytosis; recombinant granulocyte macrophage colony stimulating factor; intravenous drug administration; abdominal neoplasm; middle age; granulocyte-macrophage colony-stimulating factor; peritoneal fluid; abdominal tumor; intraperitoneal drug administration; neutrophilia; human; male; female; priority journal; article; support, non-u.s. gov't; granulocytemacrophage colony-stimulating factor; intraperitoneal infusions
Journal Title: Journal of Immunotherapy
Volume: 15
Issue: 1
ISSN: 1524-9557
Publisher: Lippincott Williams & Wilkins  
Date Published: 1994-01-01
Start Page: 59
End Page: 66
Language: English
PROVIDER: scopus
PUBMED: 8110732
DOI: 10.1097/00002371-199401000-00008
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Janice Gabrilove
    115 Gabrilove
  2. John Crown
    47 Crown
  3. Maurie Markman
    118 Markman