Phase I study of subcutaneously-administered bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor

Eur J Cancer. 1992;28(2-3):470-3. doi: 10.1016/s0959-8049(05)80078-4.

Abstract

A phase I study was initiated to test the effect of bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). 15 patients with advanced cancers were entered into the study and 14 were evaluable. Patients were administered a single subcutaneous injection (3.0-300 micrograms/m2) of rhGM-CSF. Starting at a concentration of 100 micrograms/m2, an approximate 2-fold increase in leucocyte count was noted 24 h after the injection. By 48 h the counts had returned to baseline. The 300 micrograms/m2 concentration also induced an approximate 2-fold increase. The leucocytosis was associated with a predominant increase in circulating neutrophils and bands. An increase in monocytes was also noted, but peak levels were recorded 48-72 h after the injection. At both the 100 micrograms/m2 and the 300 micrograms/m2 doses, significant levels of circulating rhGM-CSF were detected. The levels measured in the plasma of patients receiving 300 micrograms/m2 were over 10-fold greater than those measured at 100 micrograms/m2. There was no detectable antibody formation against the rhGM-CSF in any of the study patients. The drug was exceptionally well-tolerated. This study shows that rhGM-CSF can be safely administered by subcutaneous administration and a single injection is capable of inducing a leucocytosis with increased circulating neutrophils, bands, and monocytes when doses are used which result in significant levels of circulating rhGM-CSF.

Publication types

  • Clinical Trial

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Escherichia coli / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Leukocyte Count / drug effects*
  • Neoplasms / blood*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology

Substances

  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor