Auerbach, M., Silberstein, P. T., Webb, R. T., Averyanova, S., Ciuleanu, T. E., Shao, J., & Bridges, K. (2010). Darbepoetin alfa 300 or 500 µg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. American Journal of Hematology, 85, 655–663.

To evaluate the safety and efficacy of darbepoetin alfa (DA) administration every three weeks at fixed doses with or without intravenous (IV) iron.

The study used 1:1:1:1 randomization to one of four groups, stratified by platinum versus nonplatinum. The primary endpoint was hemoglobin 11 g/dL or greater, with no iron deficiency. The secondary endpoint was incidence of transfusions and change in Functional Assessment of Cancer Therapy-Fatigue (FACT-F) score from baseline to end of study. DA was administered every three weeks, and dosages were reduced according to hemoglobin levels. Weekly, 400 µg of IV iron were given, and dosages were reduced as warranted based on ferritin levels. Patients were assigned to one of four groups with or without iron with DA at either 300 µg or 500 µg.

• The study included 128 patients (78 females, 40 males).
• Age ranged from 27 to 97 years. Mean ages for the four arms were 61.7, 54.5, 64.5, and 61.8 years.
• Patients had nonmyeloid malignancies.
• Hemoglobin 10 or less
• Patients had more than eight weeks of planned chemotherapy.

• Multisite
• North America and Europe (Romania and Russia)

FACT-F

DA at 300 µg and 500 µg given every three weeks demonstrated similar benefits, and added IV iron improved treatment response. There were larger increases in hemoglobin level, and increase in hemoglobin level occurred earlier. The proportions of patients with clinically significant increases in FACT-F score were 100% for the DA 300 µg group, 64% for the 500 µg DA group, 66% for those not receiving iron, and 100% for those receiving iron. No evidence existed of a statistically significant interaction between DA dose received and IV iron usage.

Fatigue and hemoglobin levels improved in patients with anemia receiving DA with and without iron.

• No appropriate control group was used.
• Several anaphylactoid reactions to IV iron shed light on a safety issue.
• Efficacy results were pooled and summarized because no evidence was observed of a statistically significant interaction between DA and IV iron usage.

DA cannot be recommended at any dose for cancer-related fatigue.