Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma.
Macrophage colony-stimulating factor (M-CSF) is a lineage-specific, homodimeric growth factor that supports the proliferation and maturation of bone marrow progenitors and the survival and function of mononuclear/macrophage cells. In vitro studies have demonstrated antitumor activity of macrophage colony-stimulating factor-treated monocytes against melanoma target cells. A Phase I study was conducted by administering the glycosylated form of the protein to patients with metastatic melanoma as two 7-day continuous i.v. infusions separated by a 2-week rest. Cohorts of three patients per dose level received escalating doses of 10-160 microgram/kg/day. Safety, clinical, and biological effects were evaluated. The infusions were well tolerated with occasional maximum grade 2 nonhematological toxicity. Rapidly reversible thrombocytopenia was the major hematological adverse effect. Its etiology may in part be explained by proliferation and activation of monocyte/macrophage cells in bone marrow samples. Evidence for a biological effect on tumors was suggested by the delayed, complete disappearance of multiple lesions in one patient and a decrease in the size of one marker lesion in a second patient with a mixed response. Fasting serum cholesterol levels decreased during the infusions and may represent an additional therapeutic application for this growth factor.
Jakubowski
A A
AA
Departments of Medicine, Nursing, Biostatistics, and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Bajorin
D F
DF
Templeton
M A
MA
Chapman
P B
PB
Cody
B V
BV
Thaler
H
H
Tao
Y
Y
Filippa
D A
DA
Williams
L
L
Sherman
M L
ML
Garnick
M B
MB
Houghton
A N
AN
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor