title: 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.
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 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-6956, USA. jglaspy@mednet.ucla.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: Jaswant Sinh
authors.initials: JS
authors.lastname: Jadeja
authors.forename: Glen
authors.initials: G
authors.lastname: Justice
authors.forename: Alex
authors.initials: A
authors.lastname: Fleishman
authors.forename: Gregory
authors.initials: G
authors.lastname: Rossi
authors.forename: Alan B
authors.initials: AB
authors.lastname: Colowick
mesh_terms: 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
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D004921:Erythropoietin; D000077143:Docetaxel; D000068256:Darbepoetin alfa; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine