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

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Abstract
BACKGROUND Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin α, 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 nonresponders or darbepoetin α at doses of 4.5 μg/kg per week until hemoglobin concentration ≥ 12 g/dL, then 1.5 μg/kg per week (Group 1); 4.5 μg/kg per week for 4 weeks, then 2.25 μg/kg per week for 8 weeks (Group 2); or 4.5 μg/kg per week for 4 weeks, then 3.0 μg/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 α 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 α 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 α was associated with an early and maintained reduction in patient‐reported fatigue. The adverse event profile was comparable with all doses of darbepoetin α and rHuEPO. CONCLUSIONS Darbepoetin α, 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. Cancer 2003;97:1312–20. © 2003 American Cancer Society. DOI 10.1002/cncr.11186

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