Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.
J Clin Oncol
; 10(10): 1643-9, 1992 Oct.
Article
em En
| MEDLINE
| ID: mdl-1403042
ABSTRACT
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 ANDMETHODS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Macrófagos
/
Neoplasias
Limite:
Adult
/
Aged
/
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
1992
Tipo de documento:
Article
País de afiliação:
Moldávia