American Journal of Kidney Diseases
Volume 53, Issue 6 , Page 1102, June 2009

Erythropoietin and Cancer: An Old Risk

University of Messina, Messina, Italy

Article Outline

 

To the Editor:

We read with interest the December 2008 In the Literature editorial by Crowther and Radwi1 regarding a JAMA article from Bennett et al.2 We believe it is high time to put an end to any doubts that erythropoietin-stimulating agents (ESAs) are tumor-stimulating factors. In the 1960s, Leaders et al3 and Thorling4 observed that erythropoietin (EPO) stimulated the development of some tumoral forms. EPO is argued to have a role in regenerative medicine in vitro and in vivo by stimulating angiogenesis, the persistent natural regenerative activity of humans.5 Certainly EPO receptors are present on endothelial cells, which, from an ontogenetic view point, have the same precursor as erythroblasts: hemangioblasts. The presence of EPO receptors in these cells has negative consequences in the context of cancer development, but is positive in other conditions because it can protect heart, brain, and kidney tissue.6

Bennett et al2 also emphasize that therapy with ESAs induces venous thromboembolic events, but neither they nor Crowther and Radwi1 discuss thrombopoiesis as a potential mechanistic explanation. It has been observed that recombinant human EPO radiolabeled with iodine-125 binds to megakaryoblasts in bone marrow, thus confirming that specific EPO receptors are present in these cell types.7

Finally, we agree that it is of vital importance to determine the best possible approach for preventing negative effects of ESAs when administered to treat anemia in patients with cancer. We believe that transfusion therapy should be the first step in instituting therapy for anemia in patients with cancer. Only after a satisfactory hemoglobin value (∼11 g/dL) has been achieved should “nephrological” doses of ESAs be administered for the maintenance phase (50 UI/kg of EPO alfa or beta or 50 μg/kg of darbopoietin). Using this stepwise process for therapy perhaps will give us the best outcomes.

Back to Article Outline

Acknowledgements 

Financial Disclosure: None.

Back to Article Outline

References 

  1. Crowther M, Radwi G. Erythropoietin-stimulating agents: Ongoing concerns with safety. Am J Kidney Dis. 2008;52:1039–1041
  2. Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA. 2008;299:914–924
  3. Leaders FE, Dixon RL, Osborne JW, Long JP. Erythropoietic stimulating factor (ESF) as a stimulant of tumor growth. Proc Soc Exp Biol Med. 1962;110:658–660
  4. Thorling EB. On the effect of erythropoietin as an accelerant of tumour-growth. Acta Pathol Microbiol Scand. 1965;65:481–492
  5. Ribatti D, Presta M, Vacca A, et al. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood. 1999;93:2627–2636
  6. Brines M, Cerami A. Erythropoietin-mediated tissue protection: Reducing collateral damage from the primary injury response. J Intern Med. 2008;264:405–432
  7. Fraser JK, Tan AS, Lin FK, Berridge MV. Expression of specific high-affinity binding sites for erythropoietin on rat and mouse megakaryocytes. Exp Hematol. 1989;17:10–16

PII: S0272-6386(09)00599-X

doi:10.1053/j.ajkd.2009.03.006

Refers to article:

  • Erythropoietin-Stimulating Agents: Ongoing Concerns With Safety

    Mark Crowther, Ghazala Radwi
    American Journal of Kidney Diseases December 2008 (Vol. 52, Issue 6, Pages 1039-1041)

  • In Reply to ‘Erythropoietin and Cancer: An Old Risk’

    Mark Crowther
    American Journal of Kidney Diseases June 2009 (Vol. 53, Issue 6, Pages 1102-1103)

American Journal of Kidney Diseases
Volume 53, Issue 6 , Page 1102, June 2009

Article Tools