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Guidelines for the Use of Erythropoietic Proteins in Anaemic Patients with Cancer

Anaemia is a frequent finding in cancer patients and should be carefully assessed. Additional causes of anaemia such as iron deficiency, bleeding, nutritional defects or haemolysis should be corrected prior to erythropoietic protein therapy. The following recommendations are related to adult cancer patients with solid tumours or haematological malignancies:
  • In cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 90–110 g/L based on anaemia-related symptoms.
  • In patients with cancer-related anaemia not undergoing chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 90–110 g/L based on anaemia-related symptoms.
  • Erythropoietic proteins may be considered in asymptomatic, anaemic patients with a Hb level of 90–110 g/L to prevent a further decline in Hb, according to individual factors (e.g., type/intensity of chemotherapy, baseline Hb).
  • For anaemic patients who are transfusion-dependent, erythropoietic proteins should be initiated in addition to RBC transfusions.
  • We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy and/or radiotherapy who have normal Hb values at the start of treatment.
  • Elderly patients experience the same benefits from treatment with erythropoietic proteins as younger patients.
  • The target Hb concentration should be 120–130 g/L.
  • The two major goals of erythropoietic protein therapy should be to improve quality-of-life (QOL) and prevent transfusions.
  • The use of erythropoietic proteins with the aim of improving survival or response to treatment is not recommended as there is no evidence to support this. Further studies are needed.
  • Within reasonable limits of body weight, fixed doses of erythropoietic proteins should be used.
  • We recommend the dosing of erythropoietic proteins according to Fig. 1. However, the decision to dose-escalate cannot be generally recommended and must be individualised. Treatment should be continued as long as Hb levels remain </=120–130 g/L and patients show symptomatic improvement. For patients reaching the target Hb, individualised titration of lowest effective maintenance dose should be made repeatedly.
  • Despite the common use of epoetin alfa QW (40,000 IU), there is limited evidence to support this dosing schedule. The QW application of epoetin beta (30,000 IU) has been shown to be effective in patients with non-myeloid haematological malignancies. The QW administration of darbepoetin alfa (2.25 µg/kg) can be recommended. There is currently limited evidence to support the use of darbepoetin alfa in Q2W, Q3W or Q4W dosing intervals.
  • The use of higher initial doses of erythropoietic proteins can currently not be recommended as a standard approach with epoetin alfa or epoetin beta, but limited evidence exists for darbepoetin alfa. Further studies are needed.
  • There are no predictive factors of response to erythropoietic proteins that can be routinely used in clinical practice; a low serum erythropoietin (EPO) level (in particular in haematological malignancies) is the only verified predictive factor of some importance. Values must be interpreted relative to the degree of anaemia present.
  • For patients undergoing autologous blood stem cell transplants, the effects of erythropoietic proteins have not yet been convincingly shown and they cannot therefore be recommended.
  • For patients undergoing allogeneic blood stem cell transplants, the clinical impact of erythropoietic proteins is limited and they can only be recommended on an individual basis.
  • The fear of pure red cell aplasia (PRCA) should not lead to erythropoietic proteins being withheld in patients with cancer.
  • When using erythropoietic proteins to treat anaemia in cancer patients, the combined analysis of all study data indicates a slightly increased risk of thromboembolic events. However, this may be related to the target Hb level achieved.

Fig. 1

Abbreviations: Hb, haemoglobin; RBC, red blood cells; QOL, quality of life; TIW, three times per week; PRCA, pure red cell aplasia; QW, once per week; Q2W, once every 2 weeks; Q3W, once every 3 weeks.

  1. Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Osterborg A, Repetto L, Soubeyran P; European Organisation for Research and Treatment of Cancer (EORTC) Taskforce for the Elderly. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer. 2007 Jan;43(2):258-70. [Medline]
  2. Henry DH. Guidelines and recommendations for the management of anaemia in patients with lymphoid malignancies. Drugs. 2007;67(2):175-94. [Medline]

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