The initial introduction of EPOs around 1989 concerned the treatment of renal anaemia, which is caused by a deficiency in the production of endogenous EPO. In 90% to 95% of renal patients, EPO dramatically improves the quality of life. Within weeks after the start of treatment, haemoglobin and red blood cell count start to rise. This reduction in anaemia has a number of secondary effects. For example, the cardiovascular function improves, which not only enhances the feeling of wellbeing, but also reduces mortality.

The list of other beficial effects is impressive and include enhanced immune and endocrine functions, improvements in memory, concentration and other cerebral functions and decreased bleeding tendency through improved platelet function.

EPOs are also succesfully being used in the treatment of cancer-associated anaemia. In cancer, the endogenous EPO production is suppressed and EPO substitution leads to a reduction in transfusion requirements. Furthermore, in cancer patients, EPO increases the quality of life by reducing the fatigue level. This improvement is particularly notable in patients with mild anaemia, where transfusion dependency is not an issue.

The two first generations of biotechnology-derived EPOs available in Europe are epoetin alpha (Eprex) and epoetin beta (Neorecormon). These two products have an identical amino acid sequence, but they differ in glycosylation and, therefore, in isoform composition. Both are produced in Chinese hamster ovary (CHO) cells and their difference in glycosylation probably reflects a difference in the purification process. The formulation of the products is different and this can influence safety. Their pharmacokinetic characteristics are comparable and their biological and clinical efficacy are similar.

Millions of patients have been treated with recombinant EPOs in the last 20 years, and these products have been shown to be among the safest biotechnological products. The side effects seen are caused by the increase in haematocrit and not by direct toxicity of EPOs. The main side effect is hypertension, which occurs almost exclusively in renal patients during the acute reduction in anaemia and is less during the maintenance phase.

The other, more rare side effects include influenzalike symptoms and increased blood viscosity, leading to clotting of lines and vascular access thrombosis. Pure red cell aplasia (PRCA), associated with the use of subcutaneous epoetin alpha, will be discussed later. Based on animal studies, suggestions have been made as to the increase of tumour progression through EPOs. However, a careful evaluation of all available clinical data from the different manufacturers have failed to confirm this effect in cancer patients.