Abstract
Background Erythropoiesis-stimulating agents (ESAs) have been shown to reduce the need for red blood cell (RBC) transfusions and to improve quality of life for cancer patients with anaemia. However, increased risks of mortality and disease progression have been reported when using ESAs with excessive target haemoglobin levels. In 2007, the United States Food and Drug Administration and Korea Food and Drug Administration issued regulatory alerts for using ESAs in cancer patients. Objective This retrospective study was performed to evaluate changes in ESA prescribing patterns between 2006 and 2010 and the impact on RBC transfusions in patients with solid tumours. Setting The Seoul National University Hospital (SNUH) in Korea. Methods This study includes adult patients with solid tumours who were diagnosed and treated in the SNUH from January 2006 to December 2010. The exclusion criterion was concomitant chronic renal failure. The patients’ Hb levels and prescription data for ESAs and RBC transfusions were statistically analysed. The number of inpatient and outpatient solid-tumour patients was also analysed as a baseline. Main outcome measure Prescription data on ESAs and RBC transfusion. Results After adjusting for the number of patient visits, the monthly mean ESA doses dispensed decreased by an average of 1,192 mcg per quarter over the last 5 years, and the number of RBC transfusions ordered increased by 3.77 instances per quarter. After correcting for the number of patients, the mean doses of ESA dispensed each month decreased by 3,190 mcg per quarter, and the number of RBC transfusions ordered increased by 9.51 instances per quarter. Conclusion During the last 5 years, the number of ESA doses dispensed at SNUH decreased and the number of RBC transfusions at SNUH increased, independent of the number of patients. The reduction in ESA use was thought to be due to the release of the safety alert letter in 2007. However, this study did not analyse other risk factors that may have influenced the number of RBC transfusions (e.g. metastatic cancer, comorbidities, surgery). Still, the results of this study suggest that the decreased ESA doses were relevant to the increased RBC transfusions.
Similar content being viewed by others
References
Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst. 1999;91:1616–34.
Barrett-Lee PJ, Bailey NP, O’Brien ME, Wager E. Large-scale UK audit of blood transfusion requirements and anaemia in patients receiving cytotoxic chemotherapy. Br J Cancer. 2000;82:93–7.
Littlewood TJ, Bajetta E, Nortier JW, Vercammen E, Rapoport B. 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. 2001;19:2865–74.
Seidenfeld J, Piper M, Flamm C, Hasselblad V, Armitage JO, Bennett CL, et al. Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials. J Natl Cancer Inst. 2001;93:1204–14.
FDA. Postmarket drug safety information for patients and providers: information on erythropoiesis-stimulating agents (ESA) Epoetin alfa (marketed as Procrit, Epogen) Darbepoetin alfa (marketed as Aranesp); 16 Feb 2010. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm109375.htm. Accessed 9 Feb 2012.
Henke M, Laszig R, Rube C, Schafer U, Haase KD, Schilcher B, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet. 2003;362:1255–60.
Leyland-Jones B, Semiglazov V, Pawlicki M, Pienkowski T, Tjulandin S, Manikhas G, et al. 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;23:5960–72.
Wright JR, Ung YC, Julian JA, Pritchard KI, Whelan TJ, Smith C, et al. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. J Clin Oncol. 2007;25:1027–32.
Jenkins JK. FDA news and events: erythropoiesis-stimulating agents (ESA); 26 June 2007. Available at http://www.fda.gov/NewsEvents/Testimony/ucm110908.htm. Accessed 9 Feb 2012.
Korea Food and Drug Administration. ESA medicine safety letter distribution; 16 May 2007. Available at http://www.kfda.go.kr/index.kfda?mid=394&pageNo=11&seq=4178&cmd=v. Accessed 9 Feb 2012.
Korea National Statistics Office. Korea Standard Classification of Disease; 1 Jan 2011. Available at http://kostat.go.kr/kssc/stclass/StClassAction.do?method=searchDisName&classKind=5&catgrp=kssc&catid1=kssc03&catid2=kssc03b. Accessed 9 Feb 2012.
US Food and Drug Administration product label. Aranesp® (Darbepoetin alfa) For Injection; 16 Feb 2010.
Hershman DL, Buono DL, Malin J, McBride R, Tsai WY, Neugut AI. Patterns of use and risks associated with erythropoiesis-stimulating agents among medicare patients with cancer. J Natl Cancer Inst. 2009;101:1633–41.
Central Cancer Registration Office. 2008 National Cancer Statistics; 28 Dec 2010. Available at http://naver.nanet.go.kr/SearchDetailView.do?cn=MONO1201129381&sysid=nhn. Accessed 9 Feb 2012.
Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. Transfusion medicine. First of two parts–blood transfusion. N Engl J Med. 1999;340:438–47.
Faulds D, Sorkin EM. Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis. Drugs. 1989;38:863–99.
Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, et al. 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. 2007;26:132–49.
Ludwig H, Crawford J, Osterborg A, Vansteenkiste J, Henry DH, Fleishman A, et al. Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia. J Clin Oncol. 2009;27:2838–47.
Aapro M, Scherhag A, Burger HU. Effect of treatment with epoetin-beta on survival, tumour progression and thromboembolic events in patients with cancer: an updated meta-analysis of 12 randomised controlled studies including 2301 patients. Br J Cancer. 2008;99:14–22.
Vekeman F, Bookhart BK, White J, McKenzie RS, Duh MS, Piech CT, et al. Impact of limiting erythropoiesis-stimulating agent use for chemotherapy-induced anemia on the United States blood supply margin. Transfusion. 2009;49:895–902.
Ferrajoli A, Buzdar AU, Dejesus Y, Cheng L, Michaud LB, Rodriguez MA. Usage of erythropoiesis-stimulating agents in cancer patients at an academic cancer center and experience with specific care management tools for anemia. Cancer. 2011 [Epub 2011 Jan 24].
Conflicts of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kang, R.Y., Lee, J., Lee, Y.H. et al. Impact of erythropoiesis-stimulating agents on red blood cell transfusion in Korea. Int J Clin Pharm 34, 651–657 (2012). https://doi.org/10.1007/s11096-012-9660-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11096-012-9660-0