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.
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.
Hesketh
Paul J
PJ
Division of Hematology and Medical Oncology, Caritas St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA. phesketh@massmed.org
Arena
Francis
F
Patel
Dhimant
D
Austin
Matt
M
D'Avirro
Paul
P
Rossi
Gregory
G
Colowick
Alan
A
Schwartzberg
Lee
L
Bertoli
Luigi F
LF
Cole
John T
JT
Demetri
George
G
Dessypris
Emmanuel
E
Dobbs
Tracy
T
Eisenberg
Peter
P
Fleischman
Roger
R
Hall
James
J
Hoffman
Phillip C
PC
Laber
Damian A
DA
Leonard
John
J
Lester
Eric P
EP
McCachren
Spence
S
McMeekin
Scott
S
Meza
Luis
L
Miller
David Scott
DS
Nand
Sucha
S
Oliff
Ira
I
Paroly
Warren
W
Pawl
Larry
L
Perez
Alejandra
A
Raftopoulos
Harry
H
Rigas
James
J
Rowland
Kendrith
K
Scullin
Daniel C
DC
Tezcan
Haluk
H
Waples
John
J
Ward
John
J
Yee
Lorrin K
LK
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
D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa