Randomized, double-blind, placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia.
OBJECTIVE
Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA.


METHODS
Patients aged > or = 18 years with anemia (hemoglobin <11 g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive darbepoetin alfa 300 microg (n = 193) or placebo (n = 193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.


METHODS
The primary endpoint was the proportion of patients who received > or =1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration > or =11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL, and the change in hemoglobin concentration over time.


RESULTS
The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p < 0.001). There were no differences between the two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels. Study limitations suggest caution in the interpretation of these results: transfusions, the primary endpoint, were recommended but not required if hemoglobin concentrations were < or =8.0 g/dL, and protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups.


CONCLUSIONS
In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA.


BACKGROUND
Study 20030232; ClinicalTrials.Gov Identifier: NCT00110955.
Hernandez
Enrique
E
Temple University Hospital, Philadelphia, PA, USA.
Ganly
Peter
P
Charu
Veena
V
Dibenedetto
Joseph
J
Tomita
Dianne
D
Lillie
Tom
T
Taylor
Kerry
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D010919:Placebos; D055815:Young Adult
D010919:Placebos; D004921:Erythropoietin; D000068256:Darbepoetin alfa