Comparison of Darbepoetin Alfa and Epoetin Alfa for Radiotherapy(RT) or Chemoradiotherapy(CT/RT)-Induced Anemia

Abstract

Purpose/Objective: A large European Survey has shown that more than 38% of the cancer patients treated with RT were anemic (Hb<12.0g/dL) at least once during the survey. This figure reached 60–70% when patients were treated with both CT and RT1. Correction of anemia may have a positive impact on radiotherapy (RT) or chemoradiotherapy (CT/RT) treatment outcomes2,3. Both darbepoetin alpha and epoetin alpha effectively correct CT-induced anemia, but data comparing both drugs are scarce, especially on the RT setting. Objective: To compare darbepoetin alpha and epoetin alpha administered once weekly (qw) for RT-induced anemia. Materials/Methods: This is a prospective, single-institution study. Cancer patients with anemia (Hb<13g/dL men or <12g/dL women) treated with RT in our institution between 03/03 and 03/04 where consecutively assigned to receive darbepoetin alpha 150mcg/qw SC (group 1) or epoetin alpha 40.000IU/qw SC (group 2). Oral iron was administered to all patients. The dose of erythropoietic proteins (EP) was increased to 300mcg/qw (darbepoetin alpha) or 60.000IU (40.000IU + 20.000IU)/qw (epoetin alpha) in non-responders (Hb rise<1g/dL after 4 weeks). The treatment was withheld if either Hb≥15g/dL during the RT treatment or ≥14g/dl after RT. Maximum treatment duration was 16 weeks(w). Results: 125 patients (group 1, n=62; group 2, n=63) were enrolled. 81 patients received RT and 44 CT/RT. Age (mean (SD)) was 67.4(11.3)years. 67% of the patients where men. 54% were on stage III/IV. No major differences were observed between the two groups regarding tumor type, stage, previous treatments, treatment intention, or baseline Hb (mean (SD):12.1(1.3)g/dl darbepoetin alpha, 11.9 (1.3)g/dL epoetin alpha). Treatment duration was also similar for both the EP therapy (mean(SD)) (6.5(4.1)w darbepoetin alpha, 6.5(4.3)w epoetin alpha) and RT (7.1(2.1)w darbepoetin alpha, 7.1(2.6)w epoetin alpha). Comparing both groups on an intention-to-treat (ITT) basis: 64.5% of the patients in the darbepoetin alpha group and 47.6% in the epoetin alpha group reached an Hb increase≥1g/dL at 4week, but only 19.4% of darbepoetin alpha patients and 23.8% of epoetin alpha patients increased the dose. 3.2% in each group required blood transfusions. 2 patients, both in the epoetin alpha group, required to restore EP treatment after withholding it, due to reoccurrence of anemia. At the end of the treatment, the proportion of responders (Hb increase ≥2g/dl without transfusions) was 72.5% darbepoetin alpha and 66.7% epoetin alpha. The Hb rise by one month after the last EP administration was(mean(SD): 2.2(1.3)g/dL darbepoetin alpha and 2.5(1.5)g/dL epoetin alpha. 4 patients experienced cardiovascular events (2 in each group: 2 myocardial infarctions, 1 thrombophlebitis, 1 aortic aneurysm break). Conclusions: Darbepoetin alpha 150mcg/qw and epoetin alpha 40.000UI/qw are both efficacious in RT-induced anemia. At these doses, the proportion of patients achieving ≥1g/dL at 4w seems higher with darbepoetin alpha, without reaching statistical significance, therefore more studies are needed. Recently, the EORTC recommended to initiate the treatment with EP at an Hb level of 9-11g/dL based on anemia-related symptoms and the target Hb concentration was fixed in 12–13g/dL4. We have already adjusted our actual clinical practice to these guidelines. 1 Ludwig H et al. Eur J Cancer 2004;40:2293-23062 Grogan M et al. Cancer 1999,86;1528–15363 Glaser CM et al. Int J Radiation Oncology Biol Phys 2001;50:705–7154 Bokemeyer C et al. Eur J Cancer 2004;40:2201-2216