Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.
| Autor: | Sanda MG; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Yang JC, Topalian SL, Groves ES, Childs A, Belfort R Jr, de Smet MD, Schwartzentruber DJ, White DE, Lotze MT, et. al. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 1992 Oct; Vol. 10 (10), pp. 1643-9. |
| DOI: | 10.1200/JCO.1992.10.10.1643 |
| Abstrakt: | Purpose: Recombinant human macrophage colony-stimulating factor (M-CSF) has been shown to stimulate specifically macrophage lineage differentiation in vitro and to induce cells capable of antitumor activity alone or in combination with an antibody. The administration of M-CSF to mice has demonstrated antitumor therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration to patients with metastatic cancer was undertaken. Patients and Methods: M-CSF was given by intermittent intravenous bolus infusion every 8 hours for 7 days; the treatment cycle was repeated once after a week of rest. Cohorts of three patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23 patients received 27 courses of M-CSF administration. All patients had metastatic solid tumors refractory to conventional therapy, including renal cell carcinoma (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). Results: Treatment-related toxicity was minimal; five patients developed transient signs of ocular or periorbital inflammation, with iridocyclitis as the most severe manifestation. At the highest doses, platelet counts decreased with therapy (but remained > 100,000/mm3) and the absolute monocyte count increased during the course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment limited because of toxicity (iritis and malaise). Pharmacokinetic studies demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal adenopathy and multiple pulmonary metastases were observed in one patient with RCC. Conclusion: Recombinant M-CSF can be administered safely to patients with metastatic cancer at doses that demonstrate biologic activity. |
| Databáze: | MEDLINE |
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