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Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia

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Abstract

Introduction

Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis.

Materials and methods

The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11 g/dL. Epoetin-α was administered at a dose level of 3 × 10,000 U weekly as soon as Hb descended to < 13 g/dL. Dose reductions to 3 × 4,000 U and 3 × 2,000 U weekly were planned in 4-week intervals if Hb stabilised in the range of 11–13 g/dL. Upon ascending to ≥13 g/dL, epoetin was discontinued. Iron supplements of 100 mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated.

Results and discussion

Their median Hb level was 13.7 (10.9–16.2) g/dL at baseline and descended to 11.0 (7.4–13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10 g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866 U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients.

Conclusion

Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantially.

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References

  1. The NCCN Cancer- and Chemotherapy-Induced Anemia Clinical Practice Guideline in Oncology (Version 3.2009).© 2008 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed [November 18, 2008]. To view the most recent and complete version of the guideline, go online to www.nccn.org

  2. Aapro MS, Link H (2008) September 2007 update on EORTC guidelines and anemia management with erythropoiesis-stimulating agents. Oncologist 13(Suppl 3):33–36

    Article  CAS  PubMed  Google Scholar 

  3. Arcasoy MO (2008) The non-haematopoietic biological effects of erythropoietin. Br J Haematol 141:14–31

    Article  CAS  PubMed  Google Scholar 

  4. Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, Balan S, Barker L, Rana J (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 22:1301–1307

    Article  CAS  PubMed  Google Scholar 

  5. Bamias A, Aravantinos G, Kalofonos C, Timotheadou N, Siafaka V, Vlahou I, Janinis D, Pectasides D, Pavlidis N, Fountzilas G (2003) Prevention of anemia in patients with solid tumors receiving platinum-based chemotherapy by recombinant human Erythropoietin (rHuEpo): a prospective, open label, randomized trial by the Hellenic Cooperative Oncology Group. Oncology 64:102–110

    Article  CAS  PubMed  Google Scholar 

  6. Bastit L, Vandebroek A, Altintas S, Gaede B, Pinter T, Suto TS, Mossman TW, Smith KE, Vansteenkiste JF (2008) Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol 26:1611–1618

    Article  CAS  PubMed  Google Scholar 

  7. Bennett CL, Silver SM, Djulbegovic B, Samaras AT, Blau CA, Gleason KJ, Barnato SE, Elverman KM, Courtney DM, McKoy JM, Edwards BJ, Tigue CC, Raisch DW, Yarnold PR, Dorr DA, Kuzel TM, Tallman MS, Trifilio SM, West DP, Lai SY, Henke M (2008) Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 299:914–924

    Article  CAS  PubMed  Google Scholar 

  8. Bohlius J, Langensiepen S, Schwarzer G, Seidenfeld J, Piper M, Bennett C, Engert A (2005) Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Natl Cancer Inst 97:489–498

    Article  CAS  PubMed  Google Scholar 

  9. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, Piper M, Rades D, Steensma DP, Djulbegovic B, Fey MF, Ray-Coquard I, Machtay M, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A (2009) Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet 373:1532–1542

    Article  CAS  PubMed  Google Scholar 

  10. Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, Trelle S, Weingart O, Bayliss S, Djulbegovic B, Bennett CL, Langensiepen S, Hyde C, Engert A (2006) Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 98:708–714

    Article  CAS  PubMed  Google Scholar 

  11. Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Osterborg A, Repetto L, Soubeyran P (2007) EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 43:258–270

    Article  CAS  PubMed  Google Scholar 

  12. Caro JJ, Salas M, Ward A, Goss G (2001) Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 91:2214–2221

    Article  CAS  PubMed  Google Scholar 

  13. Cascinu S, Fedeli A, Del Ferro E, Luzi Fedeli S, Catalano G (1994) Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo. J Clin Oncol 12:1058–1062

    CAS  PubMed  Google Scholar 

  14. Chang J, Couture F, Young S, McWatters KL, Lau CY (2005) Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy. J Clin Oncol 23:2597–2605

    Article  CAS  PubMed  Google Scholar 

  15. Crawford J, Robert F, Perry M, Belani CP, Sarokhan B, for the Anemia Prevention in NSCLC Study Group (2003) Epoetin alfa 40,000 U once weekly maintains hemoglobin in advanced non-small-cell lung cancer patients receiving first-line chemotherapy. Proc Am Soc Clin Oncol 22:abstract 2527

    Google Scholar 

  16. Crawford J (2007) Erythropoietin: high profile, high scrutiny. J Clin Oncol 25:1021–1023

    Article  CAS  PubMed  Google Scholar 

  17. Crawford J, Robert F, Perry MC, Belani C, Williams D (2007) 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 2:210–220

    Article  PubMed  Google Scholar 

  18. de Castro J, Belda-Iniesta C, Isla D, Domine M, Sanchez A, Batiste E, Baron MG (2008) Early intervention with epoetin beta prevents severe anaemia in lung cancer patients receiving platinum-based chemotherapy: a subgroup analysis of the NeoPrevent study. Lung Cancer 59:211–218

    Article  PubMed  Google Scholar 

  19. Duh MS, Weiner JR, White LA, Lefebvre P, Greenberg PE (2008) Management of anaemia: a critical and systematic review of the cost effectiveness of erythropoiesis-stimulating agents. Pharmacoeconomics 26:99–120

    Article  PubMed  Google Scholar 

  20. Fleming TR (1982) One-sample multiple testing procedure for phase II clinical trials. Biometrics 38:143–151

    Article  CAS  PubMed  Google Scholar 

  21. Glaspy J, Bukowski R, Steinberg D, Taylor C, Tchekmedyian S, Vadhan-Raj S (1997) Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group J Clin Oncol 15:1218–1234

    CAS  Google Scholar 

  22. Groopman JE, Itri LM (1999) Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst 91:1616–1634

    Article  CAS  PubMed  Google Scholar 

  23. Hedenus M, Birgegard G, Nasman P, Ahlberg L, Karlsson T, Lauri B, Lundin J, Larfars G, Osterborg A (2007) Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study. Leukemia 21:627–632

    CAS  PubMed  Google Scholar 

  24. Henke M, Mattern D, Pepe M, Bezay C, Weissenberger C, Werner M, Pajonk F (2006) Do erythropoietin receptors on cancer cells explain unexpected clinical findings? J Clin Oncol 24:4708–4713

    Article  CAS  PubMed  Google Scholar 

  25. Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ (2008) The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol 67:39–61

    Article  PubMed  Google Scholar 

  26. Kimel M, Leidy NK, Mannix S, Dixon J (2008) 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 11:57–75

    PubMed  Google Scholar 

  27. Littlewood TJ, Bajetta E, Nortier JW, Vercammen E (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 19:2865–2874

    CAS  PubMed  Google Scholar 

  28. Ludwig H, Van Belle S, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, Kosmidis P, Krzakowski M, Nortier J, Olmi P, Schneider M, Schrijvers D (2004) The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 40:2293–2306

    Article  PubMed  Google Scholar 

  29. Marchetti M, Barosi G (2004) Clinical and economic impact of epoetins in cancer care. Pharmacoeconomics 22:1029–1045

    Article  CAS  PubMed  Google Scholar 

  30. Numico G, Garrone O, Dongiovanni V, Silvestris N, Colantonio I, Di Costanzo G, Granetto C, Occelli M, Fea E, Heouaine A, Gasco M, Merlano M (2005) Prospective evaluation of major vascular events in patients with nonsmall cell lung carcinoma treated with cisplatin and gemcitabine. Cancer 103:994–999

    Article  PubMed  Google Scholar 

  31. Pedrazzoli P, Farris A, Del Prete S, Del Gaizo F, Ferrari D, Bianchessi C, Colucci G, Desogus A, Gamucci T, Pappalardo A, Fornarini G, Pozzi P, Fabi A, Labianca R, Di Costanzo F, Secondino S, Crucitta E, Apolloni F, Del Santo A, Siena S (2008) Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol 26:1619–1625

    Article  CAS  PubMed  Google Scholar 

  32. Pirker R, Ramlau RA, Schuette W, Zatloukal P, Ferreira I, Lillie T, Vansteenkiste JF (2008) Safety and efficacy of darbepoetin alpha in previously untreated extensive-stage small-cell lung cancer treated with platinum plus etoposide. J Clin Oncol 26:2342–2349

    Article  CAS  PubMed  Google Scholar 

  33. Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, Djulbegovic B, Goode MJ, Jakubowski AA, Rarick MU, Regan DH, Lichtin AE (2008) 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 26:132–149

    Article  CAS  PubMed  Google Scholar 

  34. Schouwink JH, Codrington H, Sleeboom HP, Kerkhofs LG, Wormhoudt LW (2008) Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy. Eur J Cancer 44:819–829

    Article  CAS  PubMed  Google Scholar 

  35. Scrijvers D, Roila F (2009) Erythropoiesis-stimulating agents in cancer patients: ESMO recommendations for use. Ann Oncol 20(Suppl 4):159–161

    PubMed  Google Scholar 

  36. Seidenfeld J, Piper M, Flamm C, Hasselblad V, Armitage JO, Bennett CL, Gordon MS, Lichtin AE, Wade JL 3rd, Woolf S, Aronson N (2001) Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials. J Natl Cancer Inst 93:1204–1214

    Article  CAS  PubMed  Google Scholar 

  37. Steensma DP, Molina R, Sloan JA, Nikcevich DA, Schaefer PL, Rowland KM Jr, Dentchev T, Novotny PJ, Tschetter LK, Alberts SR, Hogan TF, Law A, Loprinzi CL (2006) Phase III study of two different dosing schedules of erythropoietin in anemic patients with cancer. J Clin Oncol 24:1079–1089

    Article  CAS  PubMed  Google Scholar 

  38. Stohlawetz PJ, Dzirlo L, Hergovich N, Lackner E, Mensik C, Eichler HG, Kabrna E, Geissler K, Jilma B (2000) Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood 95:2983–2989

    CAS  PubMed  Google Scholar 

  39. Straus DJ, Testa MA, Sarokhan BJ, Czuczman MS, Tulpule A, Turner RR, Riggs SA (2006) Quality-of-life and health benefits of early treatment of mild anemia: a randomized trial of epoetin alfa in patients receiving chemotherapy for hematologic malignancies. Cancer 107:1909–1917

    Article  CAS  PubMed  Google Scholar 

  40. Thatcher N, De Campos ES, Bell DR, Steward WP, Varghese G, Morant R, Vansteenkiste JF, Rosso R, Ewers SB, Sundal E, Schatzmann E, Stocker H (1999) Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer. Br J Cancer 80:396–402

    Article  CAS  PubMed  Google Scholar 

  41. Vandebroek A (2006) A randomized open-label study of darbepoetin alfa administered every 3 weeks with or without parenteral iron in anemic subjects with nonmyeloid malignancies receiving chemotherapy. In: A randomized open-label study of darbepoetin alfa administered every 3 weeks with or without parenteral iron in anemic subjects with nonmyeloid malignancies receiving chemotherapy

  42. Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, Bayliss S, Moss P, Stanworth S, Hyde C (2007) A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess 11:1–202, iii-iv

    CAS  PubMed  Google Scholar 

  43. Witzig TE, Silberstein PT, Loprinzi CL, Sloan JA, Novotny PJ, Mailliard JA, Rowland KM, Alberts SR, Krook JE, Levitt R, Morton RF (2005) Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol 23:2606–2617

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Ms. Julia Rengier-Styles for her excellent job in data management and review of the manuscript.

Epoetin-alpha (Eprex®) was provided by Janssen-Cilag Company. Iron (III)-hydroxide sucrose complex was provided by Vifor AG Company.

The sponsors had no role in the study design, the collection and interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication.

Conflict of interest statement

None of the authors has any financial or potential conflict of interest to disclose.

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Authors and Affiliations

  1. Centre Pluridisciplinaire d’Oncologie, University Hospital–CHUV BH06, Rue du Bugnon 46, 1011, Lausanne, Switzerland

    François Lüthi, Serge Leyvraz & Christian Monnerat

  2. Department of Oncology, University of Basel, Basel, Switzerland

    Miklos Pless, Beat Biedermann, Emilie Müller & Richard Hermann

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  1. François Lüthi
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  2. Miklos Pless
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Correspondence to Serge Leyvraz.

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François Lüthi and Miklos Pless contributed equally to the work.

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Lüthi, F., Pless, M., Leyvraz, S. et al. Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia. Support Care Cancer 18, 1515–1520 (2010). https://doi.org/10.1007/s00520-009-0773-5

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  • DOI: https://doi.org/10.1007/s00520-009-0773-5

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