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Effects of bacterially synthesized recombinant human granulocyte macrophage colony stimulating factor in patients with advanced malignancy



Effects of bacterially synthesized recombinant human granulocyte macrophage colony stimulating factor in patients with advanced malignancy



Annals of Internal Medicine 110(5): 357-364



Study Objective: To define the clinical and hematologic effects of subcutaneously administered bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Design: Single arm nonrandomized dose escalation study. Patients: Twenty-one patients with advanced malignancy who were receiving concurrent myelosuppressive therapy. Interventions: Subcutaneous administration of rhGM-CSF by once-daily injection to groups of two to four patients at doses of 0.3 to 30 .mu.g/kg body weight .cntdot. d for 10 consecutive days. Some patients received a second 10-day period of daily rhGM-CSF treatment after a 10-day nontreatment interval followed by alternate-day treatment. Clinical status and hematologic values were monitored frequently. Measurements and Main Results: All doses of rhGM-CSF caused an immediate transient fall of 84% to 99% in circulating neutrophils, eosinophils, and monocytes. Continued daily dosing caused a leukocytosis of up to 10-fold with increases in numbers of circulating neutrophils, eosinophils, monocytes, and lymphocytes. There appeared to be a plateau in the increase in neutrophils in the dose range 3 to 15 .mu.g/kg .cntdot. d. Marrow aspirates showed increased proportions of promyelocytes and myelocytes. Alternate-day injection of 15 .mu.g/kg maintained a leukocytosis. At doses up to 15 .mu.g/kg .cntdot. d, rhGM-CSF was well tolerated but adverse effects included bone pains, myalgias, rashes, and liver dysfunction. At doses exceeding 15 .mu.g/kg .cntdot. d, pericarditis was a dose-limiting toxicity. Idiopathic thrombocytopenic purpura was reactivated by rhGM-CSF in one patient. Conclusions: Bacterially synthesized rhGM-CSF induces a leukocytosis in the dose range of 3 to 15 .mu.g/kg .cntdot. d. These doses are appropriate for phase II studies.

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Accession: 007269155

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PMID: 2644886


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