Randomized, double-blind, placebo-controlled trial of every-3-week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia.

Abstract

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.

RESEARCH DESIGN AND 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.

MAIN OUTCOME MEASURES:

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.

TRIAL REGISTRATION:

Study 20030232; ClinicalTrials.Gov Identifier: NCT00110955.

• Authors: Enrique Hernandez, Peter Ganly, Veena Charu, Joseph Dibenedetto, Dianne Tomita, Tom Lillie, Kerry Taylor, ARANESP 20030232 Study Group
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 25 Issue 9 Pg. 2109-20 (Sep 2009) ISSN: 1473-4877 [Electronic] England
• PMID: 19601709 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Placebos
• Erythropoietin
• Darbepoetin alfa

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Anemia (drug therapy, etiology)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Darbepoetin alfa
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Erythropoietin (administration & dosage, analogs & derivatives)
• Female
• Humans
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Placebos
• Young Adult