Flexible dosing with Darbepoetin alfa for the treatment of chemotherapy-induced anemia

Isabelle Wauters, Karin Pat, Johan Vansteenkiste

Respiratory Oncology Unit (Pulmonology) and Leuven Lung Cancer Group, University Hospital Gasthuisberg, Catholic University, Leuven, Belgium

Abstract: Anemia is frequent in cancer patients with chemotherapy, and has an important negative effect on health-related quality of life (QoL). Darbepoetin alfa belongs to a new class of erythropoietic proteins with a unique molecular structure and interesting properties compared with classic recombinant human erythropoietin. Darbepoetin alfa is effective for chemotherapy-induced anemia when administered once weekly at a dose of 2.25 µg/kg, as shown in two large phase III placebo-controlled trials in patients with solid tumors and hematological malignancies. Furthermore, it was safe and well tolerated. More recently attention has been focused on optimizing Darbepoetin alfa therapy. Front-loaded dosing was explored to accelerate the hemoglobin (Hb) response and effect on QoL, but this idea could not be confirmed in a large phase III study. Based on the prolonged half-life of Darbepoetin alfa, administration every 3 weeks was appealing. In a large phase III trial, noninferiority of administration of 500 µg every 3 weeks compared with the weekly dosing could be confirmed, both in terms of reduction of red blood cell transfusion, Hb parameters, and QoL. This schedule is very convenient for patients and caregivers as it allows synchronization of erythropoietic therapy and common chemotherapy schedules. Questions for future study are the optimal iron supplementation strategy and the effect of Darbepoetin alfa on outcome. This article reviews the clinical development of Darbepoetin alfa with emphasis on recent data.

Keywords: Darbepoetin alfa, erythropoietic therapy, anemia, chemotherapy-induced anemia, pharmacokinetics, clinical trials, quality of life