Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer
| Autor: | E. Groves, L. Flaherty, Ta-Hsu Chou, Michael S. Simon, Manuel Valdivieso, Michael J. Kraut, Bruce G. Redman, Silvana Martino |
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| Rok vydání: | 1992 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Time Factors Bilirubin Immunology Biopterin Antineoplastic Agents Gastroenterology Neopterin Monocytes chemistry.chemical_compound Pharmacokinetics Internal medicine Neoplasms medicine Immunology and Allergy Humans Infusions Intravenous Pharmacology Creatinine medicine.diagnostic_test business.industry Monocyte Macrophage Colony-Stimulating Factor Complete blood count Cytotoxicity Tests Immunologic Recombinant Proteins Endocrinology medicine.anatomical_structure chemistry Toxicity Drug Evaluation business |
| Zdroj: | Journal of immunotherapy : official journal of the Society for Biological Therapy. 12(1) |
| ISSN: | 1053-8550 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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