Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia according to the EU regulation

Br J Cancer. 2011 Oct 25;105(9):1267-72. doi: 10.1038/bjc.2011.395. Epub 2011 Sep 29.

Abstract

Background: Erythropoietin-stimulating agents (ESAs) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia (CIA). Recent studies indicate that ESAs increase mortality and accelerate tumour progression. The studies also identify a 1.6-fold increased risk of venous thromboembolism. The ESA labelling was thus revised in Europe and the United States in 2008. This is the first randomised, phase III trial evaluating the efficacy and safety of epoetin-β (EPO), an ESA, dosed in accordance with the revised labelling, which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ≤ 10 g dl⁻¹ and that a sustained haemoglobin level of > 12 g dl⁻¹ should be avoided.

Methods: A total of 186 CIA patients (8.0 g dl⁻¹ ≤ haemoglobin ≤ 10.0 g dl⁻¹) with lung or gynaecological cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.

Results: The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl⁻¹ between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group (n=89) than in the placebo group (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality of life were not different. No significant differences in adverse events - for example, the incidence of thromboembolic events was 1.1% for each group - or the 1-year overall survival were observed between groups.

Conclusion: Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment. Further investigations are needed on the effect of ESAs on mortality.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anemia / chemically induced
  • Anemia / drug therapy*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Blood Transfusion
  • Erythropoietin / administration & dosage*
  • Erythropoietin / adverse effects
  • Erythropoietin / standards
  • Female
  • Genital Neoplasms, Female / complications
  • Genital Neoplasms, Female / drug therapy
  • Genital Neoplasms, Female / mortality
  • Hemoglobins / metabolism
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Placebos
  • Quality of Life
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / standards

Substances

  • Hemoglobins
  • Placebos
  • Recombinant Proteins
  • epoetin beta
  • Erythropoietin