Annals of Hematology

, Volume 85, Issue 2, pp 69–78 | Cite as

Recombinant human erythropoietin in the treatment of nonrenal anemia

Review Article

Abstract

Recombinant human erythropoietins (rhEPO) reliably increase hemoglobin levels in cancer patients experiencing chemotherapy-associated anemia. However, in patients with “anemia of cancer” not being treated with chemotherapy, rhEPO appears less effective. Recently, two studies have been broadly discussed which have raised concern on the concomitant use of erythropoietin and chemo- or radiation therapy in cancer patients. In addition, use of rhEPO is generally not considered cost-effective. Thus, the application of rhEPO should be limited to indications with proven clinical benefit. This review will provide an overview of the state of the art use of rhEPO in anemic patients and will discuss future developments.

Keywords

Erythropoietin Anemia Chemotherapy Cancer Bone marrow transplantation Myelodysplastic syndrome Surgery Critical care 

References

  1. 1.
    Cartwright GE, Wintrobe MM (1952) The anemia of infection. XVII. A review. Adv Intern Med 5:165–226 (abstr)PubMedGoogle Scholar
  2. 2.
    Bron D, Meuleman N, Mascaux C (2001) Biological basis of anemia. Semin Oncol 28:1–6CrossRefPubMedGoogle Scholar
  3. 3.
    Bertero MT, Caligaris-Cappio F (1997) Anemia of chronic disorders in systemic autoimmune diseases. Haematologica 82:375–381PubMedGoogle Scholar
  4. 4.
    Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL (1990) Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 322:1689–1692PubMedCrossRefGoogle Scholar
  5. 5.
    Spivak JL (1994) Cancer-related anemia: its causes and characteristics. Semin Oncol 21:3–8PubMedGoogle Scholar
  6. 6.
    Janatpour K, Holland PV (2002) Noninfectious serious hazards of transfusion. Curr Hematol Rep 1:149–155 (abstr)PubMedGoogle Scholar
  7. 7.
    Uhl L (2005) Infectious risks of blood transfusion. Curr Hematol Rep 1:156–162 (abstr)Google Scholar
  8. 8.
    Rizzo JD, Lichtin AE, Woolf SH et al (2002) Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. Blood 100:2303–2320CrossRefPubMedGoogle Scholar
  9. 9.
    Wu H, Liu X, Jaenisch R, Lodish HF (1995) Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83:59–67CrossRefPubMedGoogle Scholar
  10. 10.
    Anagnostou A, Liu Z, Steiner M et al (1994) Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 91:3974–3978PubMedCrossRefGoogle Scholar
  11. 11.
    Ribatti D, Presta M, Vacca A et al (1999) Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 93:2627–2636PubMedGoogle Scholar
  12. 12.
    Weber A, Maier RF, Hoffmann U et al (2002) Erythropoietin improves synaptic transmission during and following ischemia in rat hippocampal slice cultures. Brain Res 958:305–311CrossRefPubMedGoogle Scholar
  13. 13.
    Celik M, Gokmen N, Erbayraktar S et al (2002) Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A 99:2258–2263CrossRefPubMedGoogle Scholar
  14. 14.
    Storring PL, Tiplady RJ, Gaines Das RE et al (1998) Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties. Br J Haematol 100:79–89CrossRefPubMedGoogle Scholar
  15. 15.
    Ibbotson T, Goa KL (2001) Darbepoetin alfa. Drugs 61:2097–2104PubMedCrossRefGoogle Scholar
  16. 16.
    Rizzo JD, Lichtin AE, Woolf SH et al (2002) Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 20:4083–4107CrossRefPubMedGoogle Scholar
  17. 17.
    Witzig TE, Silberstein PT, Loprinzi CL et al (2005) Phase III, randomized, double-blind study of epoetin alfa versus placebo in anemic patients with cancer undergoing chemotherapy. J Clin Oncol 23:2606–2617CrossRefPubMedGoogle Scholar
  18. 18.
    Jadoul M, Vanrenterghem Y, Foret M, Walker R, Gray SJ (2004) Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients. Nephrol Dial Transplant 19:898–903CrossRefPubMedGoogle Scholar
  19. 19.
    Waltzman R, Williams D (2004) Head-to-head comparison of epoetin alfa (EPO) 40,000 U QW vs. darbepoetin alfa (DARB) 200 μg Q2W in anemic cancer patients receiving chemotherapy (CT): final results of a planned interim analysis (IA). Blood 104 abstract #4233Google Scholar
  20. 20.
    Glaspy JA, Jadeja JS, Justice G et al (2002) Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 87:268–276CrossRefPubMedGoogle Scholar
  21. 21.
    Glaspy JA, Jadeja JS, Justice G, Fleishman A, Rossi G, Colowick AB (2003) A randomized, active-control, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease. Cancer 97:1312–1320CrossRefPubMedGoogle Scholar
  22. 22.
    Smith KJ, Bleyer AJ, Little WC, Sane DC (2003) The cardiovascular effects of erythropoietin. Cardiovasc Res 59:538–548CrossRefPubMedGoogle Scholar
  23. 23.
    Document. Summary for basis of approval, epoetin alfa (Amgen)Google Scholar
  24. 24.
    Bohlius J, Langensiepen S, Schwarzer G et al (2004) Erythropoietin for patients with malignant disease. Cochrane Database Syst Rev CD003407Google Scholar
  25. 25.
    Besarab A, Bolton WK, Browne JK et al (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590CrossRefPubMedGoogle Scholar
  26. 26.
    Leyland-Jones B (2003) Breast cancer trial with erythropoietin terminated unexpectedly. Lancet Oncol 4:459–460CrossRefPubMedGoogle Scholar
  27. 27.
    Peces R, de la Torre M, Alcazar R, Urra JM (1996) Antibodies against recombinant human erythropoietin in a patient with erythropoietin-resistant anemia. N Engl J Med 335:523–524CrossRefPubMedGoogle Scholar
  28. 28.
    Rossert J, Casadevall N, Eckardt KU (2004) Anti-erythropoietin antibodies and pure red cell aplasia. J Am Soc Nephrol 15:398–406CrossRefPubMedGoogle Scholar
  29. 29.
    Gershon SK, Luksenburg H, Cote TR, Braun MM (2002) Pure red-cell aplasia and recombinant erythropoietin. N Engl J Med 346:1584–1586CrossRefPubMedGoogle Scholar
  30. 30.
    Bennett CL, Luminari S, Nissenson AR et al (2004) Pure red-cell aplasia and epoetin therapy. N Engl J Med 351:1403–1408CrossRefPubMedGoogle Scholar
  31. 31.
    Locatelli F, Del Vecchio L (2003) Pure red cell aplasia secondary to treatment with erythropoietin. Artif Organs 27:755–758CrossRefPubMedGoogle Scholar
  32. 32.
    Schellekens H (2002) Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther 24:1720–1740CrossRefPubMedGoogle Scholar
  33. 33.
    Casadevall N, Nataf J, Viron B et al (2002) Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 346:469–475CrossRefPubMedGoogle Scholar
  34. 34.
    Verhelst D, Rossert J, Casadevall N, Kruger A, Eckardt KU, Macdougall IC (2004) Treatment of erythropoietin-induced pure red cell aplasia: a retrospective study. Lancet 363:1768–1771CrossRefPubMedGoogle Scholar
  35. 35.
    Groopman JE, Itri LM (1999) Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 91:1616–1634CrossRefPubMedGoogle Scholar
  36. 36.
    Knight K, Wade S, Balducci L (2004) Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med 116(Suppl 7A):11S–26SCrossRefPubMedGoogle Scholar
  37. 37.
    Glaser CM, Millesi W, Kornek GV et al (2001) Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx. Int J Radiat Oncol Biol Phys 50:705–715CrossRefPubMedGoogle Scholar
  38. 38.
    Seidenfeld J, Piper M, Flamm C et al (2001) Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials. J Natl Cancer Inst 93:1204–1214CrossRefPubMedGoogle Scholar
  39. 39.
    Witzig TE, Silberstein PT, Loprinzi CL et al (2005) Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol 23:2606–2617CrossRefPubMedGoogle Scholar
  40. 40.
    Bokemeyer C, Aapro MS, Courdi A et al (2004) EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 40:2201–2216CrossRefPubMedGoogle Scholar
  41. 41.
    Dammacco F, Castoldi G, Rodjer S (2001) Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol 113:172–179CrossRefPubMedGoogle Scholar
  42. 42.
    Osterborg A, Brandberg Y, Molostova V et al (2002) Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin beta, in hematologic malignancies. J Clin Oncol 20:2486–2494CrossRefPubMedGoogle Scholar
  43. 43.
    Vansteenkiste J, Pirker R, Massuti B et al (2002) Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J Natl Cancer Inst 94:1211–1220PubMedGoogle Scholar
  44. 44.
    Hedenus M, Adriansson M, San Miguel J et al (2003) Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized, double-blind, placebo-controlled study. Br J Haematol 122:394–403CrossRefPubMedGoogle Scholar
  45. 45.
    Auerbach M, Ballard H, Trout JR et al (2004) Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol 22:1301–1307CrossRefPubMedGoogle Scholar
  46. 46.
    Ganser A (1995) Hematopoietic growth factors in the treatment of the myelodysplastic syndromes. Curr Opin Hematol 2:204–209PubMedCrossRefGoogle Scholar
  47. 47.
    Beguin Y (2002) Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica 87:1209–1221PubMedGoogle Scholar
  48. 48.
    Smith RE Jr, Tchekmedyian NS, Chan D et al (2003) A dose- and schedule-finding study of darbepoetin alpha for the treatment of chronic anaemia of cancer. Br J Cancer 88:1851–1858CrossRefPubMedGoogle Scholar
  49. 49.
    Abels RI, Larholt KM, Krantz KD, Bryant EC (1996) Recombinant human erythropoietin (rHuEPO) for the treatment of the anemia of cancer. Oncologist 1:140–150PubMedGoogle Scholar
  50. 50.
    Quirt I, Robeson C, Lau CY et al (2001) Epoetin alfa therapy increases hemoglobin levels and improves quality of life in patients with cancer-related anemia who are not receiving chemotherapy and patients with anemia who are receiving chemotherapy. J Clin Oncol 19:4126–4134PubMedGoogle Scholar
  51. 51.
    Daneryd P, Svanberg E, Korner U et al (1998) Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study. Cancer Res 58:5374–5379PubMedGoogle Scholar
  52. 52.
    Pangalis GA, Siakantaris MP, Angelopoulou MK et al (2002) Downstaging Rai stage III B-chronic lymphocytic leukemia patients with the administration of recombinant human erythropoietin. Haematologica 87:500–506PubMedGoogle Scholar
  53. 53.
    Niscola P, Scaramucci L, Bongarzoni V, Montanero M (2002) Management of disease-related anemia by high-doses of epoetin alfa in patients with multiple myeloma. Blood 100 abstract #5111 (abstr)Google Scholar
  54. 54.
    Link H, Boogaerts MA, Fauser AA et al (1994) A controlled trial of recombinant human erythropoietin after bone marrow transplantation. Blood 84:3327–3335PubMedGoogle Scholar
  55. 55.
    Vannucchi AM, Bosi A, Ieri A et al (1996) Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: a randomized trial. Bone Marrow Transplant 17:527–531PubMedGoogle Scholar
  56. 56.
    Chao NJ, Schriber JR, Long GD et al (1994) A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin’s and non-Hodgkin’s lymphoma undergoing autologous bone marrow transplantation. Blood 83:2823–2828PubMedGoogle Scholar
  57. 57.
    Ballen KK, Becker PS, Yeap BY, Matthews B, Henry DH, Ford PA (2004) Autologous stem-cell transplantation can be performed safely without the use of blood-product support. J Clin Oncol 22:4087–4094CrossRefPubMedGoogle Scholar
  58. 58.
    Biggs JC, Atkinson KA, Booker V et al (1995) Prospective randomised double-blind trial of the in vivo use of recombinant human erythropoietin in bone marrow transplantation from HLA-identical sibling donors. The Australian bone marrow transplant study group. Bone Marrow Transplant 15:129–134PubMedGoogle Scholar
  59. 59.
    A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Italian cooperative study group for rHuEpo in melodysplastic syndromes. (1998) Br J Haematol 103:1070–1074CrossRefPubMedGoogle Scholar
  60. 60.
    Terpos E, Mougiou A, Kouraklis A et al (2002) Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol 118:174–180CrossRefPubMedGoogle Scholar
  61. 61.
    Ganser A, Karthaus M (1997) Clinical use of hematopoietic growth factors in the myelodysplastic syndromes. Leuk Lymphoma 26(Suppl 1):13–27PubMedGoogle Scholar
  62. 62.
    Musto P, Lanza F, Balleari E et al (2005) Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol 128:204–209CrossRefPubMedGoogle Scholar
  63. 63.
    Rose EH, Abels RI, Nelson RA, McCullough DM, Lessin L (1995) The use of r-HuEpo in the treatment of anaemia related to myelodysplasia (MDS). Br J Haematol 89:831–837PubMedCrossRefGoogle Scholar
  64. 64.
    Negrin RS, Stein R, Doherty K et al (1996) Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 87:4076–4081PubMedGoogle Scholar
  65. 65.
    Negrin RS, Stein R, Vardiman J et al (1993) Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood 82:737–743PubMedGoogle Scholar
  66. 66.
    Hellstrom-Lindberg E, Ahlgren T, Beguin Y et al (1998) Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 92:68–75PubMedGoogle Scholar
  67. 67.
    Hellstrom-Lindberg E, Negrin R, Stein R et al (1997) Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol 99:344–351CrossRefPubMedGoogle Scholar
  68. 68.
    Casadevall N, Durieux P, Dubois S et al (2004) Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood 104:321–327CrossRefPubMedGoogle Scholar
  69. 69.
    Jadersten M, Montgomery SM, Dybedal I, Porwit-Macdonald A, Hellstrom-Lindberg E (2005) Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood Epub Apr 19; 0: 200410387Google Scholar
  70. 70.
    Thompson JA, Gilliland DG, Prchal JT et al (2000) Effect of recombinant human erythropoietin combined with granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS study group. Blood 95:1175–1179PubMedGoogle Scholar
  71. 71.
    Aloe SM, Latagliata R, Avvisati G et al (1993) Erythropoietin treatment of idiopathic myelofibrosis. Haematologica 78:371–373PubMedGoogle Scholar
  72. 72.
    Tefferi A, Silverstein MN (1994) Recombinant human erythropoietin therapy in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 86:893PubMedGoogle Scholar
  73. 73.
    Rodriguez JN, Martino ML, Dieguez JC, Prados D (1998) rHuEpo for the treatment of anemia in myelofibrosis with myeloid metaplasia. Experience in 6 patients and meta-analytical approach. Haematologica 83:616–621PubMedGoogle Scholar
  74. 74.
    Mohr B, Herrmann R, Huhn D (1993) Recombinant human erythropoietin in patients with myelodysplastic syndrome and myelofibrosis. Acta Haematol 90:65–70PubMedGoogle Scholar
  75. 75.
    Tefferi A (2003) Treatment approaches in myelofibrosis with myeloid metaplasia: the old and the new. Semin Hematol 40:18–21CrossRefPubMedGoogle Scholar
  76. 76.
    Halperin DS, Freedman MH (1989) Diamond-blackfan anemia: etiology, pathophysiology, and treatment. Am J Pediatr Hematol/Oncol 11:380–394Google Scholar
  77. 77.
    Niemeyer CM, Baumgarten E, Holldack J et al (1991) Treatment trial with recombinant human erythropoietin in children with congenital hypoplastic anemia. Contrib Nephrol 88:276–280 discussion 281.:276–80PubMedGoogle Scholar
  78. 78.
    Gillio AP, Faulkner LB, Alter BP et al (1993) Successful treatment of Diamond–Blackfan anemia with interleukin 3. Stem Cells 11(Suppl 2):123–130PubMedGoogle Scholar
  79. 79.
    Vellenga E, de Wolf JT, Halie MR (1989) Recombinant erythropoietin failed to correct anemia in Fanconi syndrome. Leukemia 3:858PubMedGoogle Scholar
  80. 80.
    Bessho M, Hirashima K, Asano S et al (1997) Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study. Multicenter study group. Eur J Haematol 58:265–272PubMedGoogle Scholar
  81. 81.
    Shao Z, Chu Y, Zhang Y, Chen G, Zheng Y (1998) Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant human granulocyte–macrophage colony-stimulating factor and erythropoietin. Am J Hematol 59:185–191CrossRefPubMedGoogle Scholar
  82. 82.
    Boschetti C, Fermo E, Bianchi P, Vercellati C, Barraco F, Zanella A (2004) Clinical and molecular aspects of 23 patients affected by paroxysmal nocturnal hemoglobinuria. Am J Hematol 77:36–44CrossRefPubMedGoogle Scholar
  83. 83.
    Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW (1993) Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N Engl J Med 328:73–80CrossRefPubMedGoogle Scholar
  84. 84.
    al Khatti A, Umemura T, Clow J et al (1988) Erythropoietin stimulates F-reticulocyte formation in sickle cell anemia. Trans Assoc Am Physicians 101:54–61PubMedGoogle Scholar
  85. 85.
    Nagel RL, Vichinsky E, Shah M et al (1993) F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study. Blood 81:9–14PubMedGoogle Scholar
  86. 86.
    Goldberg MA, Brugnara C, Dover GJ, Schapira L, Charache S, Bunn HF (1990) Treatment of sickle cell anemia with hydroxyurea and erythropoietin. N Engl J Med 323:366–372PubMedCrossRefGoogle Scholar
  87. 87.
    Rachmilewitz EA, Aker M, Perry D, Dover G (1995) Sustained increase in haemoglobin and RBC following long-term administration of recombinant human erythropoietin to patients with homozygous beta-thalassaemia. Br J Haematol 90:341–345PubMedGoogle Scholar
  88. 88.
    Nisli G, Kavakli K, Aydinok Y, Oztop S, Cetingul N, Basak N (1997) Recombinant erythropoietin trial in children with transfusion-dependent homozygous beta-thalassemia. Acta Haematol 98:199–203PubMedCrossRefGoogle Scholar
  89. 89.
    Chaidos A, Makis A, Hatzimichael E et al (2004) Treatment of beta-thalassemia patients with recombinant human erythropoietin: effect on transfusion requirements and soluble adhesion molecules. Acta Haematol 111:189–195CrossRefPubMedGoogle Scholar
  90. 90.
  91. 91.
    de Andrade JR, Jove M, Landon G, Frei D, Guilfoyle M, Young DC (1996) Baseline hemoglobin as a predictor of risk of transfusion and response to epoetin alfa in orthopedic surgery patients. Am J Orthop 25:533–542CrossRefPubMedGoogle Scholar
  92. 92.
    Epoetin alfa–product approval information (2004) http://www.fda.gov/cder/foi/label/2004/103234_5053_Epogen_lbl.pdf
  93. 93.
    Atabek U, Alvarez R, Pello MJ et al (1995) Erythropoetin accelerates hematocrit recovery in post-surgical anemia. Am Surg 61:74–77PubMedGoogle Scholar
  94. 94.
    Corwin HL, Gettinger A, Rodriguez RM et al (1999) Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double-blind, placebo-controlled trial. Crit Care Med 27:2346–2350CrossRefPubMedGoogle Scholar
  95. 95.
    Corwin HL, Gettinger A, Pearl RG et al (2002) Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA 288:2827–2835CrossRefPubMedGoogle Scholar
  96. 96.
    von Ahsen N, Muller C, Serke S, Frei U, Eckardt KU (1999) Important role of nondiagnostic blood loss and blunted erythropoietic response in the anemia of medical intensive care patients. Crit Care Med 27:2630–2639CrossRefPubMedGoogle Scholar
  97. 97.
    Vincent JL, Baron JF, Reinhart K et al (2002) Anemia and blood transfusion in critically ill patients. JAMA 288:1499–1507CrossRefPubMedGoogle Scholar
  98. 98.
    Silver DF, Piver MS (1999) Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in SCID mice bearing human ovarian cancer: a possible oxygen effect. Gynecol Oncol 73:280–284CrossRefPubMedGoogle Scholar
  99. 99.
    Thews O, Koenig R, Kelleher DK, Kutzner J, Vaupel P (1998) Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia. Br J Cancer 78:752–756PubMedGoogle Scholar
  100. 100.
    Littlewood TJ, Bajetta E, Nortier JW, Vercammen E, Rapoport B (2001) Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 19:2865–2874PubMedGoogle Scholar
  101. 101.
    Bohlius J, Langensiepen S, Schwarzer G et al (2005) Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Natl Cancer Inst 97:489–498PubMedCrossRefGoogle Scholar
  102. 102.
    Henke M, Laszig R, Rube C et al (2003) Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 362:1255–1260CrossRefPubMedGoogle Scholar
  103. 103.
    Brower V (2003) Erythropoietin may impair, not improve, cancer survival. Nat Med 9:1439CrossRefPubMedGoogle Scholar
  104. 104.
    Marchetti M, Barosi G (2004) Clinical and economic impact of epoetins in cancer care. Pharmacoeconomics 22:1029–1045PubMedCrossRefGoogle Scholar
  105. 105.
    American Society of Clinical Oncology (1996) Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. J Clin Oncol 14:671–679Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Hematology, Hemostaseology and OncologyHannover Medical SchoolHannoverGermany

Personalised recommendations