A randomized, controlled trial comparing darbepoetin alfa correction/maintenance dosing with weekly dosing for treating chemotherapy-induced anemia.
OBJECTIVE
To evaluate if a darbepoetin alfa correction/maintenance dosing regimen is non-inferior to a weekly regimen with respect to red blood cell transfusion requirements in patients with chemotherapy-induced anemia (CIA).


METHODS
In this randomized, active-controlled, double-blind phase 3 trial, CIA patients were randomized 1:1 to receive darbepoetin alfa in either a correction/maintenance schedule (4.5 microg/kg weekly for 4 weeks followed by 4.5 microg/kg every 3 weeks (Q3W)) or a weekly schedule (2.25 microg/kg weekly). The primary endpoint was the transfusion incidence during weeks 1-16. Non-inferiority was to be concluded if the upper limit of the 95% confidence interval (CI) of the difference in transfusion incidence between treatment groups was below 12.5%. Hematologic responses and safety profiles were also compared.


RESULTS
Transfusion incidence (95% CI) during weeks 1-16 was 37% (32-42) and 38% (32-43) in the weekly and correction/maintenance groups, respectively. The difference (95% CI) in transfusions was 0.4% (-7.0 to 7.8), demonstrating non-inferiority between treatment groups. Similar percentages in both groups achieved and maintained hemoglobin in a target range of 11-13 g/dL and had clinically meaningful FACT-F score improvements. The median (range) time to hemoglobin response was 10 (1-17) weeks and 12 (2-17) weeks in the weekly and correction/maintenance groups, respectively. Both groups had similar safety profiles.


CONCLUSIONS
A correction/maintenance schedule with its initial two-fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to those observed with a weekly schedule. Although correction/maintenance dosing provided no incremental clinical benefit, Q3W dosing could provide benefits of convenience and facilitate patient compliance.
Kotasek
Dusan
D
Ashford Cancer Centre, Ashford, Australia. dkotasek@acha.org.au
Canon
Jean-Luc
JL
Mateos
Maria Victoria
MV
Hedenus
Michael
M
Rossi
Greg
G
Taylor
Kerry
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D019338:Polypharmacy; D016896:Treatment Outcome
D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa