A randomized, active-control, pilot trial of front loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease

BACKGROUND. Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin a, a new erythropoietic agent, has longer serum residence time, allowing it to be administered less frequently. METHODS. Patients (n = 127) were randomized to receive study drug for 12 weeks: either rHuEPO 40,000 U with escalations to 60,000 U for nomesponders or darbepoetin a at doses of 4.5 mug/kg per week until hemoglobin concentration greater than or equal to 12 g/dL, then 1.5 mug/kg per week (Group 1); 4.5 mug/kg per week for 4 weeks, then 2.25 mug/kg per week for 8 weeks (Group 2); or 4.5 mug/kg per week for 4 weeks, then 3.0 mug/kg every 2 weeks (Group 3). Efficacy was measured using the mean change in hemoglobin level, the proportion of patients achieving a hemoglobin response, the time to response, and the mean change in Functional Assessment of Cancer Therapy-Fatigue Scale scores. Safety was assessed by reports of adverse events. RESULTS. overall, after 4 weeks of treatment, the mean change (95% confidence interval [95%CI]) in hemoglobin concentration was 0.53 g/dL (95%CI, 0.05-1.02 g/dL), 0.70 g/dL (95%CI, 0.11-1.29 g/dL), and 0.90 g/dL (95%CI, 0.47-1.33 g/dL) in darbepoetin a Groups 1, 2, and 3, respectively, and 0.39 g/dL (95%CI, - 0.22-1.00 g/dL) in the rHuEPO group. By the end of the study, the mean change (95%CI) in hemoglobin concentration was 1.35 g/dL (95%CI, 0.67-2.02 g/dL), 1.35 g/dL (95%CI, 0.57-2.12 g/dL), and 1.28 g/dL (95%CI, 0.84-1.73 g/dL) in darbepoetin a Groups 1, 2, and 3, respectively, and 1.03 g/dL (95%CI, 0.53-1.53 g/dL) in the rHuEPO group. The early erythropoietic response in patients who were treated with darbepoetin a was associated with an early and maintained reduction in patient-reported fatigue. The adverse event profile was comparable with all doses of darbepoetin a and rHuEPO. CONCLUSIONS. Darbepoetin a, given as a front-loaded dose for 4 weeks and followed by lower and/or less frequent doses, appears to be efficacious and may decrease the time to response relative to treatment with rHuEPO. (C) 2003 American Cancer Society.