Erythropoiesis-Stimulating Agents in Oncology

Author: John A. Glaspy MD 1
View More View Less
  • 1 From The Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, California.

Patients who have cancer, particularly those undergoing chemotherapy, frequently become anemic. Therapy with erythropoiesis-stimulating agents (ESAs) is associated with an increase in hemoglobin levels, a reduction in transfusion requirements, and, according to many clinical trialists and experienced clinicians, an improvement in functional status, productivity, and quality of life. Several randomized trials of ESAs in patients who have cancer have recently reported inferior outcomes in tumor progression or survival, raising appropriate concerns about the safety of ESAs in oncology. However, 3 important caveats to these reports exist. First, these clinical trials did not reflect the common use of ESAs in oncology practice (i.e., to treat, rather than prevent, anemia in patients undergoing chemotherapy). Second, the trials were seriously flawed and did not meet reasonable standards for cancer progression or survival trials. Third, during the same period, randomized trials were presented or published that showed no negative impact on tumor progression or survival; these trials have approximately the same shortcomings as trials that suggest a safety issue exists. The lack of definitive answers about the safety of ESAs for treating chemotherapy-related anemia has placed physicians, regulators, and most importantly patients in a difficult position that can only be addressed with additional data. This article reviews relevant preclinical and clinical available data to help improve understanding and guide decision making.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: John A. Glaspy, MD, Division of Hematology-Oncology, UCLA School of Medicine, 100 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90095-6956. E-mail: jglaspy@mednet.ucla.edu
  • 1.

    Bohlius J, Wilson J, Seidenfeld J. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev 2006;3:CD003407.

  • 2.

    Bohlius J, Wilson J, Seidenfeld J. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006;98:708714.

    • Search Google Scholar
    • Export Citation
  • 3.

    Crawford J, Cella D, Cleeland CS. Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy. Cancer 2002;95:888895.

    • Search Google Scholar
    • Export Citation
  • 4.

    Cella D, Zagari MJ, Vandoros C. Epoetin alfa treatment results in clinically significant improvements in quality of life in anemic cancer patients when referenced to the general population. J Clin Oncol 2003;21:366373.

    • Search Google Scholar
    • Export Citation
  • 5.

    Cella D, Kallich J, McDermott A, Xu X. The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials. Ann Oncol 2004;15:979986.

    • Search Google Scholar
    • Export Citation
  • 6.

    Berndt E, Kallich J, McDermott A. Reductions in anaemia and fatigue are associated with improvements in productivity in cancer patients receiving chemotherapy. Pharmacoeconomics 2005;23:505514.

    • Search Google Scholar
    • Export Citation
  • 7.

    Kimel M, Leidy NK, Mannix S, Dixon J. Does epoetin alfa improve health-related quality of life in chronically ill patients with anemia? Summary of trials of cancer, HIV/AIDS, and chronic kidney disease. Value Health 2008;11:5775.

    • Search Google Scholar
    • Export Citation
  • 8.

    Leyland-Jones B. Breast cancer trial with erythropoietin terminated unexpectedly. Lancet Oncol 2003;4:459460.

  • 9.

    Leyland-Jones B, Semiglazov V, Pawlicki M. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005;23:59605972.

    • Search Google Scholar
    • Export Citation
  • 10.

    Henke M, Laszig R, Rube C. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003;362:12551260.

    • Search Google Scholar
    • Export Citation
  • 11.

    Glaspy JA. Cancer patient survival and erythropoietin. J Natl Compr Canc Netw 2005;3:796804.

  • 12.

    Smith RE, Aapro MS, Ludwig H. Darbepoetin alpha for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. J Clin Oncol 2008;26:10401050.

    • Search Google Scholar
    • Export Citation
  • 13.

    Michael U, Jackisch C, Lenhard M. Epoetin-alpha reduces red blood cell transfusions (RBC) in high-risk breast cancer patients with adjuvant dose-dense, sequential chemotherapy with epirubicin (E), paclitaxel (T) and cyclophosphamide (C) (ETC) [abstract]. J Clinl Oncol 2005;23(Suppl 1):Abstract 613.

    • Search Google Scholar
    • Export Citation
  • 14.

    U.S. Food and Drug Administration. FDA Briefing Document. March 13, 2008: Oncologic Drugs Advisory Committee. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4345b2-01-FDA.pdf. Accessed May 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 15.

    U.S. Food and Drug Administration. 13 March 2008 ODAC Meeting Briefing Document: Epoetin alfa (Epogen®/PROCRIT®) and darbepoetin alfa (Aranesp®). Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4345b2-05-AMGEN.pdf. Accessed May 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 16.

    Overgaard J. Interim Analysis of DAHANCA 10. http://www.dahanca.dk/get_media_filephp?mediaid=125 2006. Accessed April 12, 2008.

  • 17.

    Overgaard J, Hoff C, Sand Hansen H. Randomized study of the importance of novel erythropoiesis stimulating protein (Aranesp®) for the effect of radiotherapy in patients with primary squamous cell carcinoma of the head and neck (HNSCC)—the Danish Head and Neck Cancer Group DAHANCA 10 rand [abstract]. Eur J Cancer 2007;5:7:Abstract 6LB.

    • Search Google Scholar
    • Export Citation
  • 18.

    Wright JR, Ung YC, Julian JA. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. J Clin Oncol 2007;25:10271032.

    • Search Google Scholar
    • Export Citation
  • 19.

    Aapro M, Leonard RC, Barnadas A. Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer receiving anthracycline- and/or taxane-based chemotherapy: results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study. J Clin Oncol 2008;26:592598.

    • Search Google Scholar
    • Export Citation
  • 20.

    Chang J, Couture F, Young S. Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. J Clin Oncol 2005;23:25972605.

    • Search Google Scholar
    • Export Citation
  • 21.

    Machtay M, Pajak TF, Suntharalingam M. Radiotherapy with or without erythropoietin for anemic patients with head and neck cancer: a randomized trial of the Radiation Therapy Oncology Group (RTOG 99-03). Int J Radiat Oncol Biol Phys 2007;69:10081017.

    • Search Google Scholar
    • Export Citation
  • 22.

    Grote T, Yeilding AL, Castillo R. Efficacy and safety analysis of epoetin alfa in patients with small-cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2005;23:93779386.

    • Search Google Scholar
    • Export Citation
  • 23.

    U.S. Food and Drug Administration. May 2007 Briefing Document. Available at: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-01-01-Amgen.pdf. Accessed May 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 24.

    Rades D, Tribius S, Yekebas EF. Epoetin alfa improves survival after chemoradiation for stage III esophageal cancer: final results of a prospective observational study. Int J Radiat Oncol Biol Phys 2006;65:459465.

    • Search Google Scholar
    • Export Citation
  • 25.

    Wilkinson PM, Antonopoulos M, Lahousen M. Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial. Br J Cancer 2006;94:947954.

    • Search Google Scholar
    • Export Citation
  • 26.

    U.S. Food and Drug Administration. May 2007 Briefing Document. Available at: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-02-FDA.pdf. Accessed May 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 27.

    U.S. Food and Drug Administration. May 2007 Supplement to Briefing Document. Available at: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-01-01-AMGEN-odac-supplement-2007.pdf. Accessed May 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 28.

    Suzuki N, Ohneda O, Takahashi S. Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality. Blood 2002;100:22792288.

    • Search Google Scholar
    • Export Citation
  • 29.

    Semenza GL. Regulation of hypoxia-induced angiogenesis: a chaperone escorts VEGF to the dance. J Clin Invest 2001;108:3940.

  • 30.

    Semenza GL. HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med 2002;8:S6267.

  • 31.

    Vaupel P, Briest S, Hockel M. Hypoxia in breast cancer: pathogenesis, characterization and biological/therapeutic implications. Wien Med Wochenschr 2002;152:334342.

    • Search Google Scholar
    • Export Citation
  • 32.

    Krishnamachary B, Berg-Dixon S, Kelly B. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 2003;63:11381143.

    • Search Google Scholar
    • Export Citation
  • 33.

    Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 2000;35:71103.

  • 34.

    Stoeltzing O, McCarty MF, Wey JS. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation. J Natl Cancer Inst 2004;96:946956.

    • Search Google Scholar
    • Export Citation
  • 35.

    Dunst J, Kuhnt T, Strauss HG. Anemia in cervical cancers: impact on survival, patterns of relapse, and association with hypoxia and angiogenesis. Int J Radiat Oncol Biol Phys 2003;56:778787.

    • Search Google Scholar
    • Export Citation
  • 36.

    Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 1999;53:113117.

    • Search Google Scholar
    • Export Citation
  • 37.

    Semenza GL. Intratumoral hypoxia, radiation resistance, and HIF-1. Cancer Cell 2004;5:405406.

  • 38.

    Teicher BA, Holden SA, al-Achi A, Herman TS. Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumor subpopulations in vivo in the FSaIIC murine fibrosarcoma. Cancer Res 1990;50:33393344.

    • Search Google Scholar
    • Export Citation
  • 39.

    Van Belle SJ, Cocquyt V. Impact of haemoglobin levels on the outcome of cancers treated with chemotherapy. Crit Rev Oncol Hematol 2003;47:111.

    • Search Google Scholar
    • Export Citation
  • 40.

    Kallinowski F, Zander R, Hoeckel M, Vaupel P. Tumor tissue oxygenation as evaluated by computerized-pO2-histography. Int J Radiat Oncol Biol Phys 1990;19:953961.

    • Search Google Scholar
    • Export Citation
  • 41.

    Fyles AW, Milosevic M, Pintilie M, Hill RP. Cervix cancer oxygenation measured following external radiation therapy. Int J Radiat Oncol Biol Phys 1998;42:751753.

    • Search Google Scholar
    • Export Citation
  • 42.

    Becker A, Stadler P, Lavey RS. Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 2000;46:459466.

    • Search Google Scholar
    • Export Citation
  • 43.

    Thews O, Kelleher DK, Vaupel P. Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors. Cancer Res 2001;61:13581361.

    • Search Google Scholar
    • Export Citation
  • 44.

    Carvalho G, Lefaucheur C, Cherbonnier C. Chemosensitization by erythropoietin through inhibition of the NF-kappaB rescue pathway. Oncogene 2005;24:737745.

    • Search Google Scholar
    • Export Citation
  • 45.

    Thews O, Koenig R, Kelleher DK. Enhanced radiosensitivity in experimental tumours following erythropoietin treatment of chemotherapy-induced anaemia. Br J Cancer 1998;78:752756.

    • Search Google Scholar
    • Export Citation
  • 46.

    Marx J. Angiogenesis. A boost for tumor starvation. Science 2003;301:452454.

  • 47.

    Vaupel P, Thews O, Mayer A. Oxygenation status of gynecologic tumors: what is the optimal hemoglobin level? Strahlenther Onkol 2002;178:727731.

    • Search Google Scholar
    • Export Citation
  • 48.

    Anagnostou A, Lee ES, Kessimian N. Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci U S A 1990;87:59785982.

    • Search Google Scholar
    • Export Citation
  • 49.

    Anagnostou A, Liu Z, Steiner M. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 1994;91:39743978.

    • Search Google Scholar
    • Export Citation
  • 50.

    Ribatti D, Presta M, Vacca A. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999;93:26272636.

    • Search Google Scholar
    • Export Citation
  • 51.

    Beleslin-Cokic BB, Cokic VP, Yu X. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood 2004;104:20732080.

    • Search Google Scholar
    • Export Citation
  • 52.

    Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res 2002;11:863871.

    • Search Google Scholar
    • Export Citation
  • 53.

    Crivellato E, Nico B, Vacca A. Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo. Leukemia 2004;18:331336.

    • Search Google Scholar
    • Export Citation
  • 54.

    Muller-Ehmsen J, Schmidt A, Krausgrill B. Role of erythropoietin for angiogenesis and vasculogenesis: from embryonic development through adulthood. Am J Physiol Heart Circ Physiol 2006;290:H331340.

    • Search Google Scholar
    • Export Citation
  • 55.

    Zwezdaryk KJ, Coffelt SB, Figueroa YG. Erythropoietin, a hypoxia-regulated factor, elicits a pro-angiogenic program in human mesenchymal stem cells. Exp Hematol 2007;35:640652.

    • Search Google Scholar
    • Export Citation
  • 56.

    Stohlawetz PJ, Dzirlo L, Hergovich N. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood 2000;95:29832989.

    • Search Google Scholar
    • Export Citation
  • 57.

    Ceelen W, Boterberg T, Smeets P. Recombinant human erythropoietin alpha modulates the effects of radiotherapy on colorectal cancer microvessels. Br J Cancer 2007;96:692700.

    • Search Google Scholar
    • Export Citation
  • 58.

    Batra S, Perelman N, Luck LR. Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival. Lab Invest 2003;83:14771487.

    • Search Google Scholar
    • Export Citation
  • 59.

    Hardee ME, Cao Y, Fu P. Erythropoietin blockade inhibits the induction of tumor angiogenesis and progression. PLoS ONE 2007;2:e549.

  • 60.

    LaMontagne KR, Butler J, Marshall DJ. Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models. Mol Cancer Ther 2006;5:347355.

    • Search Google Scholar
    • Export Citation
  • 61.

    Conti S, Guercini F, Iorio A. Low-molecular-weight heparin and cancer survival: review of the literature and pooled analysis of 1,726 patients treated for at least three months. Pathophysiol Haemost Thromb 2003;33:197201.

    • Search Google Scholar
    • Export Citation
  • 62.

    Kakkar AK, Levine MN, Kadziola Z. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 2004;22:19441948.

    • Search Google Scholar
    • Export Citation
  • 63.

    Lazo-Langner A, Goss GD, Spaans JN, Rodger MA. The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost 2007;5:729737.

    • Search Google Scholar
    • Export Citation
  • 64.

    Akl EA, van Doormaal FF, Barba M. Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. Cochrane Database Syst Rev 2007:CD006652.

    • Search Google Scholar
    • Export Citation
  • 65.

    Akl EA, Kamath G, Kim SY. Oral anticoagulation may prolong survival of a subgroup of patients with cancer: a cochrane systematic review. J Exp Clin Cancer Res 2007;26:175184.

    • Search Google Scholar
    • Export Citation
  • 66.

    Acs G, Acs P, Beckwith SM. Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 2001;61:35613565.

  • 67.

    Arcasoy MO, Amin K, Karayal AF. Functional significance of erythropoietin receptor expression in breast cancer. Lab Invest 2002;82:911918.

  • 68.

    Acs G, Zhang PJ, Rebbeck TR. Immunohistochemical expression of erythropoietin and erythropoietin receptor in breast carcinoma. Cancer 2002;95:969981.

    • Search Google Scholar
    • Export Citation
  • 69.

    Arcasoy MO, Amin K, Vollmer RT. Erythropoietin and erythropoietin receptor expression in human prostate cancer. Mod Pathol 2005;18:421430.

  • 70.

    Arcasoy MO, Amin K, Chou SC. Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia. Clin Cancer Res 2005;11:2027.

    • Search Google Scholar
    • Export Citation
  • 71.

    Saintigny P, Besse B, Callard P. Erythropoietin and erythropoietin receptor coexpression is associated with poor survival in stage I non-small cell lung cancer. Clin Cancer Res 2007;13:48254831.

    • Search Google Scholar
    • Export Citation
  • 72.

    Hardee ME, Arcasoy MO, Blackwell KL. Erythropoietin biology in cancer. Clin Cancer Res 2006;12:332339.

  • 73.

    Leo C, Horn LC, Rauscher C. Expression of erythropoietin and erythropoietin receptor in cervical cancer and relationship to survival, hypoxia, and apoptosis. Clin Cancer Res 2006;12:68946900.

    • Search Google Scholar
    • Export Citation
  • 74.

    Acs G, Chen M, Xu X. Autocrine erythropoietin signaling inhibits hypoxia-induced apoptosis in human breast carcinoma cells. Cancer Lett 2004;214:243251.

    • Search Google Scholar
    • Export Citation
  • 75.

    Sinclair AM, Todd MD, Forsythe K. Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. Cancer 2007;110:477488.

    • Search Google Scholar
    • Export Citation
  • 76.

    Elliott S, Busse L, Bass MB. Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 2006;107:18921895.

  • 77.

    Brown WM, Maxwell P, Graham AN. Erythropoietin receptor expression in non-small cell lung carcinoma: a question of antibody specificity. Stem Cells 2007;25:718722.

    • Search Google Scholar
    • Export Citation
  • 78.

    Osterborg A, Aapro M, Cornes P. Preclinical studies of erythropoietin receptor expression in tumour cells: impact on clinical use of erythropoietic proteins to correct cancer-related anaemia. Eur J Cancer 2007;43:510519.

    • Search Google Scholar
    • Export Citation
  • 79.

    Jelkmann W, Laugsch M. Problems in identifying functional erythropoietin receptors in cancer tissue. J Clin Oncol 2007;25:16271628; author reply 1628.

    • Search Google Scholar
    • Export Citation
  • 80.

    Sinclair AM, Rogers N, Busse L. Erythropoietin receptor transcription is neither elevated nor predictive of surface expression in human tumour cells. Br J Cancer 2008;98:10591067.

    • Search Google Scholar
    • Export Citation
  • 81.

    Laugsch M, Metzen E, Svensson T. Lack of functional erythropoietin receptors of cancer cell lines. Int J Cancer 2008;122:10051011.

  • 82.

    Berdel WE, Oberberg D, Reufi B, Thiel E. Studies on the role of recombinant human erythropoietin in the growth regulation of human nonhematopoietic tumor cells in vitro. Ann Hematol 1991;63:58.

    • Search Google Scholar
    • Export Citation
  • 83.

    Belda-Iniesta C, Perona R, Carpeno Jde C. Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells. Cancer Biol Ther 2007;6:16001605.

    • Search Google Scholar
    • Export Citation
  • 84.

    Feldman L, Wang Y, Rhim JS. Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells. Prostate 2006;66:135145.

    • Search Google Scholar
    • Export Citation
  • 85.

    Solar P, Feldman L, Jeong JY. Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel-resistant phenotype. Int J Cancer 2008;122:281288.

    • Search Google Scholar
    • Export Citation
  • 86.

    Jeong JY, Feldman L, Solar P. Characterization of erythropoietin receptor and erythropoietin expression and function in human ovarian cancer cells. Int J Cancer 2008;122:274280.

    • Search Google Scholar
    • Export Citation
  • 87.

    Lovey J, Bereczky B, Gilly R. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels. Strahlenther Onkol 2008;184:17.

    • Search Google Scholar
    • Export Citation
  • 88.

    Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D. Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma. Br J Cancer 2005;93:224232.

    • Search Google Scholar
    • Export Citation
  • 89.

    Yasuda Y, Musha T, Tanaka H. Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice. Br J Cancer 2001;84:836843.

    • Search Google Scholar
    • Export Citation
  • 90.

    Yoon D, Agarwal N, Prchal JT. Does erythropoietin promote tumor growth? Clin Cancer Res 2008;14:1920.

  • 91.

    Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 2001;91:22142221.

    • Search Google Scholar
    • Export Citation
  • 92.

    Blohmer JU, Dunst J, Harrison L. Cancer-related anemia: biological findings, clinical implications and impact on quality of life. Oncology 2005;1:1221.

    • Search Google Scholar
    • Export Citation
  • 93.

    Bohlius J, Piper M, Seidenfeld J. Comparative effectiveness of epoetin and darbepoetin for managing anemia in patients undergoing cancer treatment. Comparative effectiveness review number 3. Available at: http://hdl.handle.net/123456789/6875. Accessed MAy 13, 2008.

    • Search Google Scholar
    • Export Citation
  • 94.

    Lin A, Ryu J, Harvey D. Low-dose warfarin does not decrease the rate of thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy, radiation, and erythropoeitin. Gynecol Oncol 2006;102:98102.

    • Search Google Scholar
    • Export Citation
  • 95.

    Rizzo JD, Somerfield MR, Hagerty KL. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. J Clin Oncol 2008;26:132149.

    • Search Google Scholar
    • Export Citation
  • 96.

    Bokemeyer C, Aapro MS, Courdi A. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 2007;43:258270.

    • Search Google Scholar
    • Export Citation
  • 97.

    Charu V, Belani CP, Gill AN. Efficacy and safety of every-2-week darbepoetin alfa in patients with anemia of cancer: a controlled, randomized, open-label phase II trial. Oncologist 2007;12:727737.

    • Search Google Scholar
    • Export Citation
  • 98.

    Crawford J, Robert F, Perry MC. A randomized trial comparing immediate versus delayed treatment of anemia with once-weekly epoetin alfa in patients with non-small cell lung cancer scheduled to receive first-line chemotherapy. J Thorac Oncol 2007;2:210220.

    • Search Google Scholar
    • Export Citation
  • 99.

    Lyman GH, Glaspy J. Are there clinical benefits with early erythropoietic intervention for chemotherapy-induced anemia? A systematic review. Cancer 2006;106:223233.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 77 37 1
PDF Downloads 31 10 0
EPUB Downloads 0 0 0