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Every-three-week erythropoietic support during chemotherapy for cancer: current status and future issues.

Recently, it has been demonstrated that the administration of chemotherapy alters the pharmacology of erythropoietic-stimulating proteins (ESPs), such as endogenous erythropoietin and darbepoetin alfa, with an apparent decrease in clearance and substantial prolongation of half-life. This observation, coupled with the popularity of every-3-week chemotherapy regimens, makes it logical to pursue less-frequent dosing schedules for darbepoetin alfa. Two published studies have demonstrated that darbepoeitin alfa administered at a dose of 6.75 mug/kg or every 3 weeks to anemic patients with cancer is associated with improvements in hemoglobin levels. It has also been shown that dosing on the same day as chemotherapy is as efficacious and safe as dosing asynchronously in patients receiving every-3-week chemotherapy. These studies have increased our understanding of the biology of the interplay between chemotherapy, erythropoiesis, and ESPs and should facilitate the development of increasingly convenient and effective approaches to the treatment of chemotherapy-associated anemia. These insights are reviewed in this article. At the same time, evidence is accumulating that earlier initiation of ESP therapy, before severe anemia and symptoms occur, will be associated with further reduction in transfusion requirements, less patient-reported fatigue, and lower required doses of ESPs. In addition, recently presented trials have reported very important improvements in erythropoietic response to ESPs when patients with chemotherapy-associated anemia are treated with parenteral iron. The early initiation and parenteral iron initiatives pose opportunities and challenges for treatment regimens emerging from our increasing biologic understanding, and these are also reviewed.