title: Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer.
abstract: Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Harper Hospital, Detroit, Michigan 48201-0188.
authors.forename: B G
authors.initials: BG
authors.lastname: Redman
authors.forename: L
authors.initials: L
authors.lastname: Flaherty
authors.forename: T H
authors.initials: TH
authors.lastname: Chou
authors.forename: M
authors.initials: M
authors.lastname: Kraut
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: M
authors.initials: M
authors.lastname: Valdivieso
authors.forename: E
authors.initials: E
authors.lastname: Groves
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D003601:Cytotoxicity Tests, Immunologic; D004341:Drug Evaluation; D006801:Humans; D007262:Infusions, Intravenous; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy*; D019798:Neopterin; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D001708:Biopterins; D019798:Neopterin; D016173:Macrophage Colony-Stimulating Factor