Intravenous administration of recombinant human macrophage colony- stimulating factor to patients with metastatic cancer: A phase I study

M. G. Sanda, J. C. Yang, S. L. Topalian, E. S. Groves, A. Childs, R. Belfort, M. D. De Smet, D. J. Schwartzentruber, D. E. White, M. T. Lotze, S. A. Rosenberg

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23 Scopus citations


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 μg/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 μg/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.

Original languageEnglish (US)
Pages (from-to)1643-1649
Number of pages7
JournalJournal of Clinical Oncology
Issue number10
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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