A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy‐associated anemia

Abstract

Erythropoiesis‐stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy‐associated anemia (CAA). Extended‐interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly (“40K” arm), EA 80,000 U every 3 weeks (“80K”), EA 120,000 U every 3 weeks (“120K” arm), or DA 500 mcg every 3 weeks (“DA”), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient‐reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA‐approved schedules tested—weekly EA 40,000 U, and every 3 week DA 500 mcg—are reasonable standards for CAA therapy. Am. J. Hematol. 90:877–881, 2015. © 2015 Wiley Periodicals, Inc.

Severe case of fetal hemolytic disease caused by anti‐Cw requiring serial intrauterine transfusions complicated by pancytopenia and cholestasis

“…Darbepoetin alfa binds to the erythropoietin (EPO) receptor of erythroid progenitor cells and stimulates RBC production and differentiation. It has a longer terminal half‐life than epoetin alfa due to an altered glycosylation pattern . Follow‐up laboratory evaluation of the patient revealed an unconjugated and conjugated hyperbilirubinemia (maximum conjugated bilirubin 3.7 mg/dL, >50% of total serum bilirubin), discolored feces, elevated liver enzymes, and excessively elevated (maximum level 3455 mg/mL) serum ferritin levels.…”

Prolonged Duration of Erythropoiesis-Stimulating Agents’ Action Delays Disease Progression in Anti-Thy 1 Antibody-Induced Chronic Glomerulonephritis Rats

“…In the treatment of anemia by EPO, prolonging the duration of action through divided administration is important for maintaining a sufficient level of hemoglobin (Hb). It has been demonstrated that EPO administered at low doses in 1 week intervals is more effective than a high dose with 3-week intervals in cancer chemotherapy-associated anemia patients even if the overall total dosage is the same [6]. Likewise, increasing the half-life time of EPO in blood, for example, by integrating a methoxy-polyethylene glycol polymer chain, leading to a prolonged duration of action, is effective for hematopoiesis [3].…”