Pharmacokinetic evaluation of darbepoetin alfa for the treatment of pediatric patients with chemotherapy‐induced anemia

BACKGROUND: Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent darbepoetin alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of darbepoetin alfa in pediatric patients with CIA. PROCEDURE: Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of darbepoetin alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of darbepoetin alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. RESULTS: After a single dose of darbepoetin alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of darbepoetin alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, darbepoetin alfa was well tolerated; some study patients experienced increases in hemoglobin. CONCLUSIONS: The pharmacokinetic profile of darbepoetin alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA.