Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.
Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results.
Boogaerts
Marc
M
University Hospital Gasthuisberg, Leuven, Belgium. marc.boogaerts@uz.kuleuven.ac.be
Mittelman
Moshe
M
Vaupel
Peter
P
D000747:Anemia, Hypochromic / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002493:Central Nervous System Diseases / Q000150:complications*; D017024:Chemotherapy, Adjuvant; D003071:Cognition / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications*; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D010865:Pilot Projects; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin