Anaemia is frequently diagnosed in patients with
cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic
proteins in anaemic patients with
cancer (see ). Level I evidence exists for a positive impact of erythropoietic
proteins on haemoglobin (Hb) levels when administered to patients with
chemotherapy-induced anaemia or anaemia of
chronic disease, when used to prevent
cancer anaemia, in patients undergoing
cancer surgery and following allogeneic
bone marrow transplantation. The Hb level at which erythropoietic
protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with
chemotherapy-induced anaemia or anaemia of
chronic disease enrolled patients with a Hb concentration </=105 g/L, but none compared the effect of different baseline Hb levels on the response to treatment. Similarly, several studies defined the target Hb concentration as 120-130 g/L following treatment with erythropoietic
proteins, but none specifically addressed the correlation between target Hb level and clinical benefit in a randomised fashion. Level I evidence shows that red blood cell (RBC) transfusion requirements are significantly reduced with erythropoietic
protein therapy in patients with
chemotherapy-induced anaemia or when used to prevent
cancer anaemia (approximately 20% reduction compared with controls). We found indirect Level I and III evidence that patients with
chemotherapy-induced anaemia or anaemia of
chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase (absolute increases in response rate ranged from 8% to 18%). However, none of these studies examined the effect on response rates of a longer treatment period at the lower dose, or performed a randomised comparison of a dose increase versus an unchanged dose. There is Level I evidence to show that quality-of-life (QOL) is significantly improved in patients with
chemotherapy-induced anaemia and in those with anaemia of
chronic disease, particularly in patients achieving a Hb response to erythropoietic
protein therapy. There are insufficient data to determine the effect on survival following treatment with erythropoietic
proteins in conjunction with
chemotherapy or
radiotherapy. There is Level I evidence that dosing of erythropoietic
proteins less frequently than three times per week (TIW) is efficacious when used to treat
chemotherapy-induced anaemia or prevent
cancer anaemia. There is Level III evidence that initial doses of erythropoietic
proteins considered to be higher than current standard practice produce higher haematological responses in patients with
chemotherapy-induced anaemia or anaemia of
chronic disease. Level I evidence demonstrates that several baseline patient parameters (e.g., low endogenous
erythropoietin [EPO] concentration, age <60 years, Hb concentration >/=90 g/L) impact upon the response to erythropoietic
proteins when used to treat
chemotherapy-induced anaemia or prevent
cancer anaemia. Evidence indicates that endogenous EPO concentration impacts on response in patients with lymphoproliferative
malignancies, but is not a valid parameter in patients with solid tumours. There is Level I evidence that fixed doses of erythropoietic
proteins can be used at the start of
therapy to treat patients with
chemotherapy-induced anaemia, but maintenance doses should be titrated individually. There is no evidence that
pure red cell aplasia (PRCA) occurs following treatment with erythropoietic
proteins in patients with
chemotherapy-induced anaemia or when used prophylactically in patients with
cancer. There is Level I evidence that the risk of thromboembolic events and
hypertension are slightly elevated in patients with
chemotherapy-induced anaemia receiving erythropoietic
proteins. Level I evidence supports the effectiveness of erythropoietic
proteins to prevenroteins to prevent anaemia in non-anaemic
cancer patients receiving
chemotherapy or
radiotherapy or in those undergoing
cancer surgery. However, these are non-licensed indications and we do not currently recommend the prophylactic use of erythropoietic
proteins to prevent anaemia in patients who have normal Hb values at the start of treatment. Additional trials are warranted, especially on the issues of
iron replacement and cost-effectiveness of erythropoietic
protein therapy, as well as on tumour response/progression and survival.