title: A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies.
abstract: BACKGROUND
  The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading).
  
  
  METHODS
  During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 microg (n = 122) or at a weight-based dose of 4.5 microg/kg (n = 120) once weekly until they achieved a hemoglobin concentration > or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase).
  
  
  RESULTS
  Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed.
  
  
  CONCLUSIONS
  Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.
authors.affiliation: Division of Hematology and Medical Oncology, Caritas St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA. phesketh@massmed.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.forename: Francis
authors.initials: F
authors.lastname: Arena
authors.forename: Dhimant
authors.initials: D
authors.lastname: Patel
authors.forename: Matt
authors.initials: M
authors.lastname: Austin
authors.forename: Paul
authors.initials: P
authors.lastname: D'Avirro
authors.forename: Gregory
authors.initials: G
authors.lastname: Rossi
authors.forename: Alan
authors.initials: A
authors.lastname: Colowick
authors.forename: Lee
authors.initials: L
authors.lastname: Schwartzberg
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Bertoli
authors.forename: John T
authors.initials: JT
authors.lastname: Cole
authors.forename: George
authors.initials: G
authors.lastname: Demetri
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dessypris
authors.forename: Tracy
authors.initials: T
authors.lastname: Dobbs
authors.forename: Peter
authors.initials: P
authors.lastname: Eisenberg
authors.forename: Roger
authors.initials: R
authors.lastname: Fleischman
authors.forename: James
authors.initials: J
authors.lastname: Hall
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: Damian A
authors.initials: DA
authors.lastname: Laber
authors.forename: John
authors.initials: J
authors.lastname: Leonard
authors.forename: Eric P
authors.initials: EP
authors.lastname: Lester
authors.forename: Spence
authors.initials: S
authors.lastname: McCachren
authors.forename: Scott
authors.initials: S
authors.lastname: McMeekin
authors.forename: Luis
authors.initials: L
authors.lastname: Meza
authors.forename: David Scott
authors.initials: DS
authors.lastname: Miller
authors.forename: Sucha
authors.initials: S
authors.lastname: Nand
authors.forename: Ira
authors.initials: I
authors.lastname: Oliff
authors.forename: Warren
authors.initials: W
authors.lastname: Paroly
authors.forename: Larry
authors.initials: L
authors.lastname: Pawl
authors.forename: Alejandra
authors.initials: A
authors.lastname: Perez
authors.forename: Harry
authors.initials: H
authors.lastname: Raftopoulos
authors.forename: James
authors.initials: J
authors.lastname: Rigas
authors.forename: Kendrith
authors.initials: K
authors.lastname: Rowland
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Scullin
authors.forename: Haluk
authors.initials: H
authors.lastname: Tezcan
authors.forename: John
authors.initials: J
authors.lastname: Waples
authors.forename: John
authors.initials: J
authors.lastname: Ward
authors.forename: Lorrin K
authors.initials: LK
authors.lastname: Yee
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy*; D001835:Body Weight; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa