Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma Journal Article


Authors: Jakubowski, A. A.; Bajorin, D. F.; Templeton, M. A.; Chapman, P. B.; Cody, B. V.; Thaler, H.; Tao, Y.; Filippa, D. A.; Williams, L.; Sherman, M. L.; Garnick, M. B.; Houghton, A. N.
Article Title: Phase I study of continuous-infusion recombinant macrophage colony-stimulating factor in patients with metastatic melanoma
Abstract: 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 μg/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.
Keywords: adult; clinical article; aged; clinical trial; melanoma; metastasis; thrombocytopenia; cholesterol; phase 1 clinical trial; recombinant colony stimulating factor 1; human; male; female; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 2
Issue: 2
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 1996-02-01
Start Page: 295
End Page: 302
Language: English
PUBMED: 9816172
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus