Ask The Expert: Question Archive

Question
Regarding the pharmacodynamics of erythropoiesis-stimulating agents (ESAs), how can clinicians achieve optimal erythropoietin serum levels in patients with adequate stored iron? Given that it may be wasteful to over saturate the receptors, should clinicians aim for continual saturation of the receptor or intermittent binding to maximize their response? Additionally, are weekly therapies given over multiple doses more effective than the once-a-week administration?

NAAC Expert Response
Exploring these questions is important because erythropoietin not only increases erythropoiesis but also promotes the release of inflammatory cytokines. Toxicity occurring with ESAs has more to do with dose than with the resulting increased hematocrit. The recent Bohlius meta-analysis¹ of ESA-use in anemic cancer patients indicated that three-times-weekly administration was less harmful than once- or twice-weekly administration. I suspect that this is the case because larger doses given less frequently exceed erythropoietin receptor saturation. For a many patients, 30,000-45,000 units per week is probably optimal, particularly when given in 3 divided doses. This should yield a serum erythropoietin level of about 100 mU/mL that should not exceed receptor saturation. Intermittent administration also avoids plasma hormone accumulation.

References

1. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, Piper M, Rades D, Steensma DP, Djulbegovic B, Fey MF, Ray-Coquard I, Machtay M, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009 May 2;373(9674):1532-42. Link.
2. Spivak JL, Gascón P, Ludwig H. Anemia Management in Oncology and Hematology. Oncologist. 2009;14 Suppl 1:43-56. Link.

Last Updated: October 21, 2009