Background: Intravenous (i.v.) iron supplementation significantly improves the response to erythropoiesis-stimulating agent (ESA)-based therapies in patients with cancer- or chemotherapy-induced anemia. The economic implications of adding i.v. iron to ESA treatment are less well investigated. Published randomized controlled trials do not provide sufficient data for a comprehensive cost-effectiveness analysis. Methods: Preliminary cost calculations from the Swiss health care system perspective based on a meta-analysis and published results of eight randomized controlled trials without correction for decreased ESA need provide a conservative cost-effectiveness estimate. Results: The additional total cost of i.v. iron supplementation ranged from EUR 417 to EUR 901 per patient depending on the evaluated iron-carbohydrate complex. Considering a 24% absolute increase in the proportion of ESA responders, the incremental cost-effectiveness ratios per additional responder are EUR 1,704–3,686. In routine practice, better values may be achieved due to ESA dose savings. Conclusion: Supplementation of ESAs with i.v. iron appears to be an economically viable treatment option in anemic cancer patients. Additional research on ESA dose savings and cost-effectiveness is required.

1.
Ludwig H, Van BS, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, Kosmidis P, Krzakowski M, Nortier J, Olmi P, Schneider M, Schrijvers D: 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 2004;40:2293–2306.
2.
Nissenson AR, Wade S, Goodnough T, Knight K, Dubois RW: Economic burden of anemia in an insured population. J Manag Care Pharm 2005;11:565–574.
3.
Ershler WB, Chen K, Reyes EB, Dubois R: Economic burden of patients with anemia in selected diseases. Value Health 2005;8:629–638.
4.
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;15:979–986.
5.
Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, Bayliss S, Moss P, Stanworth S, Hyde C: 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 2007;11:1-202, iii–iv.
6.
Wolowacz SE, Cameron DA, Tate HC, Bagust A: Docetaxel in combination with doxorubicin and cyclophosphamide as adjuvant treatment for early node-positive breast cancer: a cost-effectiveness and cost-utility analysis. J Clin Oncol 2008;26:925–933.
7.
Bokemeyer C, Aapro MS, Courdi A, Foubert J, Link H, Osterborg A, Repetto L, Soubeyran P: EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer 2007;43:258–270.
8.
National Comprehensive Cancer Network: NCCN Practice Guidelines in Oncology: Cancer and Chemotherapy-Induced Anemia – v.2.2010. 2010. http://www.nccn.org/professionals/physician_gls/PDF/anemia.pdf (accessed May 6, 2010).
9.
Committee for Medicinal Products for Human Use (CHMP): Conclusions from the Committee for Medicinal Products for Human Use (CHMP) – review of safety of erythropoiesis stimulating agents (ESAs) in patients with anaemia resulting from renal insufficiency or chemotherapy in cancer patients. 2008. http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con023076.pdf.
10.
US Food and Drug Administration (FDA): FDA Drug Safety Communication: Erythropoiesis-Stimulating Agents (ESAs) – Procrit, Epogen and Aranesp. 2010. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm.
11.
Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, Balan S, Barker L, Rana J: 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 2004;22:1301–1307.
12.
Auerbach M, Silberstein PT, Webb RT, Averyanova S, Ciuleanu TE, Shao J, Bridges K: Darbepoetin alfa 300 or 500 ug once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. Am J Hematol 2010;85:655–663.
13.
Bastit L, Vandebroek A, Altintas S, Gaede B, Pinter T, Suto TS, Mossman TW, Smith KE, Vansteenkiste JF: 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 2008;26:1611–1618.
14.
Beguin Y, Maertens J, De Prijck B, Schots R, Frere P, Bonnet C, Hafraoui K, Willems E, Vanstraelen G, Lejeune M, Theunissen K, Fillet G, Baron F: Darbepoetin-Alfa and i.v. iron administration after autologous hematopoietic stem cell transplantation: a prospective randomized multicenter trial (abstract). Blood 2008;112:54.
15.
Beguin Y, Lybaert W, Bosly A: A prospective observational study exploring the impact of iron status on response to darbepoetin alfa in patients with chemotherapy induced anemia (abstract). Blood 2009;114:2007.
16.
Hedenus M, Birgegard G, Nasman P, Ahlberg L, Karlsson T, Lauri B, Lundin J, Larfars G, Osterborg A: 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 2007;21:627–632.
17.
Henry DH, Dahl NV, Auerbach M, Tchekmedyian S, Laufman LR: Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 2007;12:231–242.
18.
Pedrazzoli P, Farris A, Del PS, Del GF, Ferrari D, Bianchessi C, Colucci G, Desogus A, Gamucci T, Pappalardo A, Fornarini G, Pozzi P, Fabi A, Labianca R, Di CF, Secondino S, Crucitta E, Apolloni F, Del SA, Siena S: Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol 2008;26:1619–1625.
19.
Gafter-Gvili A, Rozen-Zvi B, Vidal L, Gafter U, Vansteenkiste JF, Shpilberg O: Intravenous iron supplementation for the treatment of cancer-related anemia – systematic review and meta-analysis (abstract). Blood 2010;116:4249.
20.
Steensma DP, Sloan JA, Dakhil SR, Dalton R, Kahanic SP, Prager DJ, Stella PJ, Rowland KM Jr, Novotny PJ, Loprinzi CL: Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia. J Clin Oncol 2011;29:97–105.
21.
Swiss tariff list – Tarmed. 2011. http://onb.tarmedsuisse.ch/ (accessed May 16, 2011).
22.
Hedenus M, Nasman P, Liwing J: Economic evaluation in Sweden of epoetin beta with intravenous iron supplementation in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy. J Clin Pharm Ther 2008;33:365–374.
23.
Auerbach M, Ballard H: Intravenous iron in oncology. J Natl Compr Canc Netw 2008;6:585–592.
24.
Dangsuwan P, Manchana T: Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecol Oncol 2010;116:522–525.
25.
Kim YT, Kim SW, Yoon BS, Cho HJ, Nahm EJ, Kim SH, Kim JH, Kim JW: Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecol Oncol 2007;105:199–204.
26.
National Comprehensive Cancer Network: NCCN Practice Guidelines in Oncology: Cancer and Chemotherapy-Induced Anemia – v.2.2011. 2011. http://www.nccn.org/professionals/physician_gls/PDF/anemia.pdf (accessed May 6, 2010).
27.
Aapro M, Beguin Y, Birgegard G, Gascon P, Hedenus M, Osterborg A: Too low iron doses and too many dropouts in negative iron trial? J Clin Oncol 2011, DOI: 10.1200/JCO. 2011.35.3219.
28.
Auerbach M, Glaspy J: What is the right balance between iron and erythropoiesis stimulating agents in chemotherapy induced anemia? Eur J Clin Med Oncol 2009;1:7–12.
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