0839 Possible adverse effects of erythropoietin-induced correction of anaemia

In a recent medicine safety communication to health professionals, the manufacturer of one of the forms of recombinant erythropoietin drew attention to concerns surrounding adverse effects of pharmacological correction of anaemia in cancer and renal failure patients. Previous summaries in this series (0702 and 0707) have dealt with the latter situation, referring in particular to a debate that raged between the Lancet and the New England Journal of Medicine, and which sought to clarify cardiovascular and mortality risks associated with correction of anaemia to a level above 115g/l. The final word seemed to be that higher Hb levels are potentially harmful, and while one may again ask why it has taken a drug manufacturer so long to include the information in its package insert, one must at least appreciate that they have done so. The debate also included discussion on whether it was the Hb elevation that conveyed the risk or the erythropoietin dose required to achieve that elevation. This introduces the question of what else erythropoietin, and pharmacological doses in particular, might be doing, and relates to the medicine safety alert which comments on adverse effects such as shortened time to tumour progression, reduced survival and risk of venous thromboembolism. Much has been written about the non-haematological effects of erythropoietin and the tissues in/on which these effects may be mediated. Erythropoietin and its receptor have been identified in the CNS, endothelial cells, liver, uterus and in solid tumours, and there is therefore the possibility that in cancer patients erythropoietin signalling might promote tumour growth e.g. via the induction of cell proliferation or angiogenesis. In vitro studies of childhood solid tumours have demonstrated erythropoietin expression in neuroblastoma, Ewing’s sarcoma, brain tumours, Wilms tumour, rhabdomyosarcoma, hepatoblastoma and in cell lines derived from these tumours. Expression was hypoxia-inducible, and addition of exogenous erythropoietin increased expression of anti-apoptotic genes, angiogenic growth factors, and endothelial growth factor.

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