R E V I E W S Darbepoetin alpha in the treatment of cancer chemotherapy-induced anemia Alberto Grossi1 Francesca Balestri2 Simone Santini3 1IstitutoLeonardo da Vinci – Hematology, Florence, Italy; 2Blood Transfusion Center, Azienda Sanitaria 4, Prato, Italy; 3Oncology Unit, Azienda Sanitaria 4, Prato, Italy Correspondence: Alberto Grossi IstitutoLeonardo da Vinci – Hematology, Via Colletta 2/r - 50136 Florence, Italy Tel +39 33 8520 0467 Fax+39 05 524 8230 Email alberto_grossi @libero.it Abstract: Anemia is a common, but underestimated and undertreated, complication of patients with cancer receiving chemo- or radiotherapy, and negatively affects their quality of life (QoL). Erythropoietic proteins (EPS) offer an effective treatment of cancer anemia and ameliorate QoL, although their use requires the correct targeting of hemoglobin increase to avoid thromboembolic complications. Currently the effort is focused on offering patients this effective treatment with reduced frequency of administration. Higher weekly single doses of recombinant human Epo (rHuEpo) either alpha or beta, instead of three times per week, have been proposed for the treatment. The pharmacokinetic and pharmacodynamic characteristics of the hyperglycosylated protein darbepoetin alpha permit even longer intervals between administrations. Every other week or every three weeks schedules have shown results (erythropoietic response, reduction of transfusion requirements, and improvement of QoL) comparable with those of weekly rHuEpo. Keywords: cancer anemia, recombinant human Epo, darbepoetin alpha Introduction Anemia is a frequent complication in patients with cancer and affects quality of life (QoL) (Cella 1997; Harper and Littlewood 2005) in at least 50%. Correct investigation of the reasons underlying anemia is mandatory for an adequate treatment (Figure 1). A recent large survey (Ludwig et al 2004) has shown that prevalence and incidence were 39.3% of 14 912 enrolled and 57.3% of 13 628 analyzed patients respectively. Only 38.9% received a treatment of either transfusions or replacement therapy including recombinant human Epo (rHuEpo). Therefore an adequate treatment is not adopted in the majority patients with anemia of cancer. A major step in the evaluation of anemia of chronic disorders, including cancer, was the recognition that erythropoietin production is often blunted and serum level inadequate to the degree of hemoglobin decrease because of toxicity, especially when platinum is used in therapy, or the disease itself (Figure 1). Therefore, the availability of rHuEpo alpha and beta, and successively darbepoetin alpha, has offered an effective alternative to red cell transfusion in this setting. Bohlius and colleagues (2005) carried out a metanalysis of 27 randomized controlled trials, involving 3953 patients, that compared the use of rHuEpo and darbepoetin (plus transfusion if needed) with observation until red blood cell transfusion was required. This study was recently updated (Bohlius et al 2006) to include 57 trials with 9353 patients. The analysis of data indicates that administration of EPS reduces the relative risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline hemoglobin below 12 g/dL (mild anemia) there is strong evidence of improved hematological response and suggestive evidence of amelioration of QoL. On the other hand, the relative risk for thromboembolic complications increases by the treatment, while it remains uncertain whether and how rHuEpo and darbepoetin Therapeutics and Clinical Risk Management 2007:3(2) 269–275 © 2007 Dove Medical Press Limited. All rights reserved 269