carried out in a subset of patients indicated that endogenous erythropoietin concentration increases and lasts for approximately 1 week following chemotherapy administration; b) synchronous administration of darbepoetin alpha was associated with a 1.3-fold increase in the darbepoetin alpha area-under-the-curve compared with asynchronous administration. The feasibility of the Q3W schedule has been confirmed by Boccia and colleagues (2006) A direct comparison between fixed 500 µ g Q3W at fixed dose and 2.25 µ g/kg QW was carried out by Canon and colleagues (2006) in a non inferiority study active-controlled phase III study, in patients with nonmyeloid malignancies. The incidence of transfusion was 19% of 353 patients in the group treated with 500 mg Q3W and 28% of 352 patient in the QW group. The target hemoglobin level was reached in a similar proportion of patients and increase in FACT-F score was also superimposable, without differences in toxicity. An Q4W administration is probably possible using an adequate dosing of darbepoetin (Smith et al 2003). A hyperglycosylated analog of darbepoetin (AMG 114) with longer half life is currently in phase I clinical study. Conclusions Anemia is a common, underestimated and undertreated complication of cancer, especially in patients treated with chemotherapy. Provided that other factors, especially iron, are in sufficient amount to support their activity, EPS offer a simple, effective and generally safe treatment of anemia. The targets of this treatment should be: a) reduction or, possibly, elimination of transfusion support (therefore the beginning of treatment should not be delayed if the patient’s hemoglobin levels is 10–11 g/dL; b) an adequate hemoglobin level (12–13 g/dL) that also would also improve QoL could be improved in patients with cancer, but avoiding higher values that could expose the patient to thromboembolic complication. The guidelines released by EORTC, NCCN, and ASCO are useful tools for these purposes. From the large amount of data available in the literature it can be concluded that darbepoetin is as effective as rHuEpo (60% to 80% of patients respond to therapy) in stimulating er ythropoiesis in patients with cancer. Pharmakokinetic characteristics make darbepoetin ideal for a reduced frequency of administration and more convenient for the patient by adjusting dosage and frequency to reach and maintain the target hemoglobin level. In consideration that chemotherapy is most commonly given every three Therapeutics and Clinical Risk Management 2007:3(2) Darbepoetin in anemia of cancer week, a supplemental Biologics License Application has been submitted by the producer to the Food and Drug Administration for Q3W administration. The European Agency (EMEA) has granted darbepoetin approval for extended dosing once every three weeks interval in the treatment of cancer chemotherapy-induced anemia in 2004. In this setting there is no evidence that 500 µ g are more effective than 300 µ g in the Q3W schedule because a direct comparison of these doses is not available. Less frequent dosing of rHuEpo, either alpha or beta, than 3 times per week proved to be effective, and adequate dosing could make the Q3W interval possible even with these erythropoietic agents. The preliminary data of efficacy of the new pegylated Epo beta (Continuous Erythropoiesis Stimulating Activity – CERA) (Osterborg et al 2004) in a Q3W administration, and the pharmacokinetics of hematide, confirm the trend toward a reduced frequency of administration of erythropoietic proteins. The development of drugs targeting the hypoxia-inducible factor through the inactivation of the degradation enzyme prolyl-4-hydroxylase and with different (oral) route of administration are underway and could offer new perspectives in the control of anemia of cancer patients. Disclosures Alberto Grossi is consultant for Shire Italia. References Alessandrino EP, Amadori S, Barosi G, et al. 2002. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica, 87:1286-306. Arcasoy MO, Amin K, Chou SC, et al. 2005. Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia. Clin Cancer Res, 11:20-7. Auerbach M, Ballard H, Trout JR, et al. 2004. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. 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