The role of human recombinant erythropoietin in treatment of anemia in cancer patients Review article
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Published:
Mar 31, 2017
Keywords:
erythropoietin, anaemia, cancer, chemotherapy
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Abstract
Anaemia is one of the most frequent results of the hematopoietic system disorder in cancer. At the time of cancer diagnosis, it is observed in 30% of untreated patients, and in 60–70% of patients receiving chemotherapy or radiotherapy. The choice of treatment for anaemia depends on the severity of disorder, the type of therapy and clinical symptoms, and may include watchful waiting, recombinant erythropoietin injection or red blood cell transfusion. Erythropoietin is a glycoprotein hormone synthesized in physiological conditions by interstitial cells of the kidney (approx. 90%). In routine medical practice, 3 kinds of human recombinant erythropoietin are used, which demonstrate a similar mechanism of action. These are erythropoietin α, erythropoietin β and darbapoietin α. The use of recombinant human erythropoietin may also be associated with measurable therapeutic benefits manifested by an increased response of cancer cells to cytotoxic drugs. However, their use is associated with a high risk of complications, including thromboembolic events. The risk results from the presence of cancer and accompanying thrombocythemia, a history of undergone surgical operations, prolonged immobilization, hypertension and thrombophlebitis.
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Kubiatowski , T., & Jankowski, T. (2017). The role of human recombinant erythropoietin in treatment of anemia in cancer patients. Medycyna Faktow (J EBM), 10(1(34), 14-21. Retrieved from https://journalsmededu.pl/index.php/jebm/article/view/2163
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References
1. Czyż A.: Powikłania hematologiczne. W: Krzakowski M., Potemski P., Warzocha K., Wysocki P. (red.): Onkologia Kliniczna. Via Medica, Gdańsk 2014.
2. Ludwig H., Van Belle S., Barrett-Lee P. et al.: 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(15): 2293-2306.
3. Wilson J., Yao G.L., Raftery J. et al.: 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(13): 1-202.
4. Radziwon P.: Dlaczego warto rozważyć stosowanie leków stymulujących erytropoezę w niedokrwistości u chorych na nowotwory. Medycyna Faktów 2016; 4(33): 357-364.
5. Prada-Turska J., Paluszkiewicz P.: Leki wpływające na czynność krwiotwórczą szpiku. W: Rajtar-Cynke G. (red.): Farmakologia. Wydawnictwo Lekarskie PZWL, Warszawa 2015.
6. Littlewood T.J., Bajetta E., Nortier J.W. et al.; Epoetin Alfa Study Group: 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(11): 2865-2874.
7. Tonia T., Mettler A., Robert N. et al.: Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst. Rev. 2012; 12: CD003407.
8. Foubert J.: New EORTC guidelines for the treatment of anaemia in patients with cancer: Implications for nursing practice. Eur. J. Oncol. Nurs. 2006; 10: 177-186.
9. Schrijvers D., De Samblanx H., Roila F.; on behalf of the ESMO Guidelines Working Group: Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use. Ann. Oncol. 2010; 21(supl. 5): v244-v247.
10. Rizzo D.J., Brouwers M., Hurley P. et al.: American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer. J. Clin. Oncol. 2010; 28(33): 4996-5010.
11. Cancer and chemotherapy-induced anemia [online: www.nccn.org].
12. Bennett C.L., Silver S.M., Djulbegovic B. et al.: Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299(8): 914-924.
13. Bennett S.L., Henke M., Lai S.Y.: Erythropoiesis-stimulating agents in the treatment of cancer-related anemia-reply. JAMA 2008; 300: 2855-2857.
14. Bohlius J., Schmidlin K., Brillant C. et al.: Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta- analysis of randomised trials. Lancet 2009; 373(9674): 1532-1542.
15. Tonelli M., Hemmelgarn B., Reiman T. et al.: Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ 2009; 180(11): E62-71.
16. Engert A., Josting A., Haverkamp H. et al.: Epoetin alfa in patients with advanced-stage Hodgkin’s lymphoma: results of the randomized placebo- controlled GHSG HD15EPO trial. J. Clin. Oncol. 2010; 28(13): 2239-2245.
17. Glaspy J., Crawford J., Vansteenkiste J. et al.: Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br. J. Cancer 2010; 102(2): 301-315.
18. Ludwig H., Crawford J., Osterborg 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(17): 2838-2847.
19. Moebus V., Jackisch C., Lueck H.J. et al.: Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J. Clin. Oncol. 2010; 28(17): 2874-2880.
20. Untch M., Fasching P.A., Konecny G.E. et al.; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators: PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer – results at the time of surgery. Ann. Oncol. 2011; 22(9): 1988-1998.
21. Untch M., von Minckwitz G., Konecny G.E. et al.: PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin – cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer – outcome on prognosis. Ann. Oncol. 2011; 22(9): 1999-2006.
22. Grote T., Yeilding A.L., Castillo R. et al.: 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(36): 9377-9386.
23. Pirker R., Ramlau R.A., Schuette W. et al.: Safety and efficacy of darbepoetin alpha in previously untreated extensive-stage small-cell lung cancer treated with platinum plus etoposide. J. Clin. Oncol. 2008; 26(14): 2342-2349.
24. Heit J.A., Silverstein M.D., Mohr D.N. et al.: Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch. Intern. Med. 2000; 160(6): 809-815.
25. Khorana A.A., Francis C.W., Culakova E. et al.: Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J. Thromb. Haemost. 2007; 5(3): 632-634.
26. Levine M.N., Gent M., Hirsh J. et al.: The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. N. Engl. J. Med. 1988; 318(7): 404-407.
27. Lyman G.H., Khorana A.A., Falanga A. et al.; American Society of Clinical Oncology: American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J. Clin. Oncol. 2007; 25(34): 5490-5505.
28. Saphner T., Tormey D.C., Gray R.: Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J. Clin. Oncol. 1991; 9(2): 286-294.
29. Glaspy J., Crawford J., Vansteenkiste J. et al.: Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br. J. Cancer 2010; 102: 301-315.
30. Besarab A., Bolton W.K., Browne J.K. et al.: 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. 1998; 339(9): 584-590.
31. Besarab A., Goodkin D.A., Nissenson A.R.; Normal Hematocrit Cardiac Trial Authors: The normal hematocrit study – follow-up. N. Engl. J. Med. 2008; 358(4): 433-434.
32. Imai E., Yamamoto R., Suzuki H., Watanabe T.: Incidence of symptomatic stroke and cancer in chronic kidney disease patients treated with epoetins. Clin. Exp. Nephrol. 2010; 14(5): 445-452.
33. Pfeffer M.A., Burdmann E.A., Chen C.Y. et al.; TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N. Engl. J. Med. 2009; 361(21): 2019-2032.
34. Seliger S.L., Zhang A.D., Weir M.R. et al.: Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease. Kidney Int. 2011; 80(3): 288-294.
35. Singh A.K., Szczech L., Tang K.L. et al.; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N. Engl. J. Med. 2006; 355(20): 2085-2098.
36. Debeljak N., Solár P., Sytkowski A.J.: Erythropoietin and cancer: the unintended consequences of anemia correction. Front. Immunol. 2014; 5: 563.
37. Sytkowski A.J.: Erythropoietin: Blood, Brain and Beyond. Wiley-VCH, Weinheim 2004.
38. Barquilla A., Pasquale E.B.: Eph receptors and ephrins: therapeutic opportunities. Annu. Rev. Pharmacol. Toxicol. 2015; 55: 465-487.
39. Gokmen-Polar Y., Toroni R.A., Hocevar B.A. et al.: Dual targeting of EphA2 and ER restores tamoxifen sensitivity in ER/EphA2-positive breast cancer. Breast Cancer Res. Treat. 2011; 127: 375-384.
40. Lu M., Miller K.D., Gokmen-Polar Y. et al.: EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity. Cancer Res. 2003; 63: 3425-3429.
41. Zhuang G., Brantley-Sieders D.M., Vaught D. et al.: Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res. 2010; 70: 299-308.
42. Li J.L., Sainson R.C., Oon C.E. et al.: DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo. Cancer Res. 2011; 71: 6073-6083.
43. Stahl S., Kaminskyy V.O., Efazat G. et al.: Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412. Cell Death Dis. 2013; 4: e454.
2. Ludwig H., Van Belle S., Barrett-Lee P. et al.: 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(15): 2293-2306.
3. Wilson J., Yao G.L., Raftery J. et al.: 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(13): 1-202.
4. Radziwon P.: Dlaczego warto rozważyć stosowanie leków stymulujących erytropoezę w niedokrwistości u chorych na nowotwory. Medycyna Faktów 2016; 4(33): 357-364.
5. Prada-Turska J., Paluszkiewicz P.: Leki wpływające na czynność krwiotwórczą szpiku. W: Rajtar-Cynke G. (red.): Farmakologia. Wydawnictwo Lekarskie PZWL, Warszawa 2015.
6. Littlewood T.J., Bajetta E., Nortier J.W. et al.; Epoetin Alfa Study Group: 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(11): 2865-2874.
7. Tonia T., Mettler A., Robert N. et al.: Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst. Rev. 2012; 12: CD003407.
8. Foubert J.: New EORTC guidelines for the treatment of anaemia in patients with cancer: Implications for nursing practice. Eur. J. Oncol. Nurs. 2006; 10: 177-186.
9. Schrijvers D., De Samblanx H., Roila F.; on behalf of the ESMO Guidelines Working Group: Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use. Ann. Oncol. 2010; 21(supl. 5): v244-v247.
10. Rizzo D.J., Brouwers M., Hurley P. et al.: American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer. J. Clin. Oncol. 2010; 28(33): 4996-5010.
11. Cancer and chemotherapy-induced anemia [online: www.nccn.org].
12. Bennett C.L., Silver S.M., Djulbegovic B. et al.: Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299(8): 914-924.
13. Bennett S.L., Henke M., Lai S.Y.: Erythropoiesis-stimulating agents in the treatment of cancer-related anemia-reply. JAMA 2008; 300: 2855-2857.
14. Bohlius J., Schmidlin K., Brillant C. et al.: Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta- analysis of randomised trials. Lancet 2009; 373(9674): 1532-1542.
15. Tonelli M., Hemmelgarn B., Reiman T. et al.: Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ 2009; 180(11): E62-71.
16. Engert A., Josting A., Haverkamp H. et al.: Epoetin alfa in patients with advanced-stage Hodgkin’s lymphoma: results of the randomized placebo- controlled GHSG HD15EPO trial. J. Clin. Oncol. 2010; 28(13): 2239-2245.
17. Glaspy J., Crawford J., Vansteenkiste J. et al.: Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br. J. Cancer 2010; 102(2): 301-315.
18. Ludwig H., Crawford J., Osterborg 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(17): 2838-2847.
19. Moebus V., Jackisch C., Lueck H.J. et al.: Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J. Clin. Oncol. 2010; 28(17): 2874-2880.
20. Untch M., Fasching P.A., Konecny G.E. et al.; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators: PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer – results at the time of surgery. Ann. Oncol. 2011; 22(9): 1988-1998.
21. Untch M., von Minckwitz G., Konecny G.E. et al.: PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin – cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer – outcome on prognosis. Ann. Oncol. 2011; 22(9): 1999-2006.
22. Grote T., Yeilding A.L., Castillo R. et al.: 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(36): 9377-9386.
23. Pirker R., Ramlau R.A., Schuette W. et al.: Safety and efficacy of darbepoetin alpha in previously untreated extensive-stage small-cell lung cancer treated with platinum plus etoposide. J. Clin. Oncol. 2008; 26(14): 2342-2349.
24. Heit J.A., Silverstein M.D., Mohr D.N. et al.: Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch. Intern. Med. 2000; 160(6): 809-815.
25. Khorana A.A., Francis C.W., Culakova E. et al.: Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J. Thromb. Haemost. 2007; 5(3): 632-634.
26. Levine M.N., Gent M., Hirsh J. et al.: The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. N. Engl. J. Med. 1988; 318(7): 404-407.
27. Lyman G.H., Khorana A.A., Falanga A. et al.; American Society of Clinical Oncology: American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J. Clin. Oncol. 2007; 25(34): 5490-5505.
28. Saphner T., Tormey D.C., Gray R.: Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J. Clin. Oncol. 1991; 9(2): 286-294.
29. Glaspy J., Crawford J., Vansteenkiste J. et al.: Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br. J. Cancer 2010; 102: 301-315.
30. Besarab A., Bolton W.K., Browne J.K. et al.: 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. 1998; 339(9): 584-590.
31. Besarab A., Goodkin D.A., Nissenson A.R.; Normal Hematocrit Cardiac Trial Authors: The normal hematocrit study – follow-up. N. Engl. J. Med. 2008; 358(4): 433-434.
32. Imai E., Yamamoto R., Suzuki H., Watanabe T.: Incidence of symptomatic stroke and cancer in chronic kidney disease patients treated with epoetins. Clin. Exp. Nephrol. 2010; 14(5): 445-452.
33. Pfeffer M.A., Burdmann E.A., Chen C.Y. et al.; TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N. Engl. J. Med. 2009; 361(21): 2019-2032.
34. Seliger S.L., Zhang A.D., Weir M.R. et al.: Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease. Kidney Int. 2011; 80(3): 288-294.
35. Singh A.K., Szczech L., Tang K.L. et al.; CHOIR Investigators: Correction of anemia with epoetin alfa in chronic kidney disease. N. Engl. J. Med. 2006; 355(20): 2085-2098.
36. Debeljak N., Solár P., Sytkowski A.J.: Erythropoietin and cancer: the unintended consequences of anemia correction. Front. Immunol. 2014; 5: 563.
37. Sytkowski A.J.: Erythropoietin: Blood, Brain and Beyond. Wiley-VCH, Weinheim 2004.
38. Barquilla A., Pasquale E.B.: Eph receptors and ephrins: therapeutic opportunities. Annu. Rev. Pharmacol. Toxicol. 2015; 55: 465-487.
39. Gokmen-Polar Y., Toroni R.A., Hocevar B.A. et al.: Dual targeting of EphA2 and ER restores tamoxifen sensitivity in ER/EphA2-positive breast cancer. Breast Cancer Res. Treat. 2011; 127: 375-384.
40. Lu M., Miller K.D., Gokmen-Polar Y. et al.: EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity. Cancer Res. 2003; 63: 3425-3429.
41. Zhuang G., Brantley-Sieders D.M., Vaught D. et al.: Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res. 2010; 70: 299-308.
42. Li J.L., Sainson R.C., Oon C.E. et al.: DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo. Cancer Res. 2011; 71: 6073-6083.
43. Stahl S., Kaminskyy V.O., Efazat G. et al.: Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412. Cell Death Dis. 2013; 4: e454.