title: Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia according to the EU regulation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Respiratory Medicine, Osaka Medical College Hospital, Osaka, Japan. fujisaka_y@dotd.med.kindai.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Fujisaka
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Nagase
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: M
authors.initials: M
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: N
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001803:Blood Transfusion; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D005260:Female; D005833:Genital Neoplasms, Female / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards
chemical_list: D006454:Hemoglobins; D010919:Placebos; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin