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 alpha, 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 alpha at doses of 4.5 microg/kg per week until hemoglobin concentration >or= 12 g/dL, then 1.5 microg/kg per week (Group 1); 4.5 microg/kg per week for 4 weeks, then 2.25 microg/kg per week for 8 weeks (Group 2); or 4.5 microg/kg per week for 4 weeks, then 3.0 microg/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 alpha 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 alpha 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 alpha was associated with an early and maintained reduction in patient-reported fatigue. The adverse event profile was comparable with all doses of darbepoetin alpha and rHuEPO.


CONCLUSIONS
Darbepoetin alpha, 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.
Glaspy
John A
JA
Division of Hematology/Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-6956, USA. jglaspy@mednet.ucla.edu
Jadeja
Jaswant Sinh
JS
Justice
Glen
G
Fleishman
Alex
A
Rossi
Gregory
G
Colowick
Alan B
AB
D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D000068256:Darbepoetin alfa; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005221:Fatigue / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010865:Pilot Projects; D043823:Taxoids; D016896:Treatment Outcome; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D004921:Erythropoietin; D000077143:Docetaxel; D000068256:Darbepoetin alfa; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine