Comparison of 4- and 24-hour intravenous infusion schedules for granulocyte-macrophage colony-stimulating factor.

Abstract

We evaluated the toxicity, pharmacokinetics, and biologic activity of 4- versus 24-h intravenous infusions of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) in patients with advanced malignancy. The doses of rhuGM-CSF evaluated were 1, 3, 5, and 10 μg/kg administered by 4- or 24-h infusion for 10 days. A total of 32 patients was treated (17, 4-h infusion ; 15, 24-h infusion). Toxicities seen with both schedules included fever, chills, nausea, emesis, fatigue, and pain. Other observations in the 4-h infusion group included pulmonary edema and bone pain and in the 24-h infusion group, leukocytosis and atrial fibrillation. Pharmacokinetic data for the 4-h infusion showed C max and area under the curve (AUC) increased with dose, and the terminal elimination half-life varied from 0.7 to 1.1 h. Comparative pharmacokinetic assessment of the 24-h infusion was difficult because of low steady-state plasma concentrations. Hematologic effects in the 24-h infusion group included a dose-dependent increase in total white blood cells and absolute granulocyte count, generally greater than those in the 4-h infusion group. In summary, a greater biologic effect occurred in the 24-h infusion group than in the 4-h infusion group. The toxicity profile differed slightly between the 4- and 24-h infusion groups, but both were generally well tolerated by patients.