Venous thromboembolism risk and erythropoiesis-stimulating agents for the treatment of cancer-associated anemia: A meta-analysis

Tumor Biology

Volumn 35, Issue 1, 2014, Pages 603-613

  Gao, Sheng ^a   Ma, Jing Jing ^a   Lu, Cheng ^a  

^a WOMEN S HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

Author keywords

Anemia; Cancer; Darbepoetin; Erythropoiesis stimulating agents; Erythropoietin; Meta analysis; Venous thromboembolism

Indexed keywords

ANTIANEMIC AGENT; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PLACEBO; RECOMBINANT ERYTHROPOIETIN;

ANEMIA; ARTICLE; BREAST CANCER; CANCER ASSOCIATED ANEMIA; CANCER CHEMOTHERAPY; CANCER PALLIATIVE THERAPY; CANCER RADIOTHERAPY; CARDIOVASCULAR RISK; CHEMORADIOTHERAPY; HEAD AND NECK CANCER; HEMATOLOGIC MALIGNANCY; HUMAN; INCIDENCE; LUNG CANCER; MEDLINE; META ANALYSIS; META ANALYSIS (TOPIC); OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PUBLISHING; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; SAMPLE SIZE; SOLID TUMOR; SYSTEMATIC REVIEW; UTERINE CERVIX CANCER; VENOUS THROMBOEMBOLISM;

ANEMIA; CLINICAL TRIALS, PHASE III AS TOPIC; HEMATINICS; HUMANS; INCIDENCE; NEOPLASMS; ODDS RATIO; PUBLICATION BIAS; RISK; VENOUS THROMBOEMBOLISM;

EID: 84896714514     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-013-1084-5     Document Type: Article

References (70)

1. Bokemeyer C,Oechsle K, Hartmann J-T. Anaemia in cancer patients: pathophysiology, incidence and treatment. Eur J Clin Invest. 2005;35 Suppl 3:26-31.
2. Ludwig H, van Belle S, Barrett-Lee P, Birgegard G, Bokemeyer C, Gascon P, et al. The European Cancer Anemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anemia in cancer patients. Eur J Cancer. 2004;40:2293-306.
3. Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systematic, quantitative review. Cancer. 2001;91:2214-21.
4. Seidenfeld J, Piper M, Flamm C, et al. Epoetin treatment of anemia associated with cancer therapy: a systematic review and metaanalysis of controlled clinical trials. J Natl Cancer Inst. 2001;93: 1204-14.
5. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006;98:708-14.
6. Wilson J, Yao GL, Raftery J, et al. A systematic reviewand economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. 2007;11:1-220.
7. Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst. 2008;100:1155-66.
8. Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAM.A. 2008;299:914-24.
9. Henke M, Mattern D, Pepe M, et al. Do erythropoietin receptors on cancer cells explain unexpected clinical findings? J Clin Oncol. 2006;24:4708-13.
10. FDA briefing document. Safety concerns associated with Aranesp (darbepoetin alfa) Amgen, Inc. and Procrit (epoetin alfa) Ortho Biotech, L.P., for the treatment of anemia associated with cancer chemotherapy. Hearings before the Subcommittee on Oncologic Drugs Advisory Committee, Center for Drug Evaluation and Research. http://www.fda.gov/ohrms/dockets/ac/04/briefing/4037B2- 04-FDA-Aranesp-Procrit.htm#-ednref45 (2008).
11. Brower V. ESAs further restricted, but debate continues. J Natl Cancer Inst. 2008;100:1344-51.
12. The Cochrane Collaboration. Review Manager (RevMan) [computer program].Version 5.0. Copenhagen: The Nordic Cochrane Centre; 2008.
13. DerSimonian R, LairdN.Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-88.
14. Higgins JP, Thompson SG. Quantifying heterogeneity in a metaanalysis. Stat Med. 2002;21:1539-58.
15. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088-101.
16. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test.BMJ. 1997;315:629-34.
17. Aapro M, Leonard RC, Barnadas A, Marangolo M, Untch M, Malamos N, et al. 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(4):592-8.
18. Amgen DA 145 Study. April 19, 2007. http://wwwext.amgen.com/media/media- pr-detail.jsp?year=2007&releaseID=987476 (2008).
19. Abels R. Erythropoietin for anaemia in cancer patients. Eur J Cancer. 1993;29A suppl 2:S2-8.
20. Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, et al. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011;29(28):3791-7.
21. Bamias A, Aravantinos G, Kalofonos C, et al. 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. 2003;64(2):102-10.
22. Cabanillas ME, Kantarjian H, Thomas DA, Mattiuzzi GN, Rytting ME, Bruera E, et al. Epoetin alpha decreases the number of erythrocyte transfusions in patients with acute lymphoblastic leukemia, lymphoblastic lymphoma, and Burkitt leukemia/lymphoma: results of a randomized clinical trial. Cancer. 2012;118(3):848-55.
23. Cascinu S, Fedeli A, Del Ferro E, Luzi Fedeli S, Cat-alano G. Recombinant human erythropoietin treatment in cisplatin-associated anemia: a randomized, double-blind trial with placebo. J Clin Oncol. 1994;12(5):1058-62.
24. Case Jr DC, Bukowski RM, Carey RW, et al. Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. J Natl Cancer Inst. 1993;85(10):801-6.
25. Dammacco F, Castoldi G, Rodjer S. Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma. Br J Haematol. 2001;113(1):172-9.
26. Debus JHS, Morr H, Mezger J, Sebastian M, Angermund R, Drings P. Epoetin alfa (EPO) and survival in patients with non-resectable NSCLC-interim results. German Medical Science. http://www.egms.de/en/meetings/dkk2006/06dkk257.shtml (2007).
27. FDA briefing document. May 10, 2007: Oncologic Drugs Advisory Committee. Continuing reassessment of the risks of erythropoiesisstimulating agents (ESAs) administered for the treatment of anemia associated with cancer chemotherapy. http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-02-FDA.pdf (2008).
28. Fujisaka Y, Sugiyama T, Saito H, Nagase S, Kudoh S, EndoM, et al. Randomised, phase III trial of epoetin-β to treat chemotherapyinduced anaemia according to the EU regulation. Br J Cancer. 2011;105(9):1267-72.
29. Gupta S, Singh PK, Bisth SS, BhattML, Pant M, Gupta R, et al. Role of recombinant human erythropoietin in patients of advanced cervical cancer treated "by chemoradiotherapy". Cancer Biol Ther. 2009;8(1):13-7.
30. Grote T, Yeilding AL, 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):9377-86.
31. Gordon DH, Nichols G, Ben-Jacob A, et al. Treating anemia of cancer with darbepoetin alfa adminis-tration every 4 weeks: final results from a phase 2, randomized, double-blind, placebocontrolled study in cancer patients not receiving chemotherapy and/ or radiotherapy. Presented at American Society of Hematology; December 9, 2006; Orlando, FL; Abstract 1304.
32. Hernandez E, Ganly P, Charu V, Dibenedetto J, Tomita D, Lillie T, et al. Randomized, double-blind, placebo-controlled trial of every-3- week darbepoetin alfa 300 micrograms for treatment of chemotherapy-induced anemia. Curr Med Res Opin. 2009;25(9):2109-20.
33. Hoskin PJ, Robinson M, SlevinN, Morgan D, HarringtonK, Gaffney C. Effect of epoetin alfa on survival and cancer treatment-related anemia and fatigue in patients receiving radical radiotherapy with curative intent for head and neck cancer. J Clin Oncol. 2009;27(34):5751-6.
34. Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet. 2003;362(9392):1255-60.
35. Henry DH, Abels RI. Recombinant human erythropoietin in the treatment of cancer and chemotherapy-induced anemia: results of double-blind and open-label follow-up studies. Semin Oncol. 1994;21 suppl 3:21-8.
36. Leyland-Jones B, Semiglazov V, Pawlicki M, 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(25):5960-72.
37. Littlewood TJ, Bajetta E, Nortier JW, Vercam-men 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(11):2865-74.
38. Machtay M, Pajak TF, SuntharalingamM, et al. 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(4):1008-17.
39. Osterborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma-a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma. Blood. 1996;87(7):2675-82.
40. Osterborg A, Brandberg Y, Hedenus M. Impact of epoetin-beta on survival of patients with lymphoproliferative malignancies: longterm follow up of a large randomized study. Br J Haematol. 2005;129(2):206-9.
41. Pirker R, Ramlau RA, Schuette W, Zatloukal P, Ferreira I, Lillie T, 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):2342-9.
42. Pronzato P, Cortesi E, van der Rijt CC, Bols A,Moreno-Nogueira JA, de Oliveira CF, et al. Epoetin alfa improves anemia and anemiarelated, patient-reported outcomes in patients with breast cancer receivingmyelotoxic chemotherapy: results of a European, multicenter, randomized, controlled trial. Oncologist. 2010;15(9):935-43.
43. Razzouk BI, Hockenberry M, Hinds PS, Rackoff W, Hord JD. A double-blind, placebo-controlled study of once-weekly epoetin alfa in children with cancer undergoing myelosuppressive chemotherapy. J Clin Oncol. 22:14S. June 5, 2004. Presented at the 40th Annual Meeting of the American Society of Clinical Oncology; June 5-8, 2004; New Orleans, LA; Abstract 8527.
44. Rose ERK, Revicki D, Brown R, Reblando J. Clinical and health status assessments in anemic chronic lymphocytic leukemia (CLL) patients treated with epoetin alfa (EPO). Blood. 1994;4 suppl 1:526a.
45. Rosenzweig MQ, Bender CM, Lucke JP, Yasko JM, Brufsky AM. The decision to prematurely terminate a trial of R-HuEPO due to thrombotic events. J Pain Symptom Manage. 2004;27(2):185-90.
46. Ray-Coquard I, Dussart S, Goillot C, Mayeur D, Debourdeau P, Ghesquieres H, et al. A risk model for severe anemia to select cancer patients for primary prophylaxis with epoetin alpha: a prospective randomized controlled trial of the ELYPSE study group. Ann Oncol. 2009;20(6):1105-12.
47. Savonije JVGC, Van Bochove A, Pinedo H, Giaccone G. Early intervention with epoetin-alfa during platinum-based chemotherapy. J Clin Oncol. 22:14S. June 5, 2004. Presented at the 40th Annual Meeting of the American Society of Clinical Oncology; June 5-8, 2004; New Orleans, LA; Abstract 8111.
48. Smith Jr RE, Tchekmedyian NS, Chan D, et al. A dose- and schedulefinding study of darbepoetin alpha for the treatment of chronic anaemia of cancer. Br J Cancer. 2003;88(12):1851-8.
49. Ten Bokkel Huinink WW, de Swart CA, van Toorn DW, et al. Controlledmulticentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy. Med Oncol. 1998;15(3):174-82.
50. Thatcher N, De Campos ES, Bell DR, et al. Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer. Br J Cancer. 1999;80(3-4):396-402.
51. Throuvalas N, Antonadou D, Boufi M, Lavey R. Erythropoietin decreases transfusion requirements during radiochemotherapy. Paper presented at the 36th Annual Meeting of the American Society of Clincial Oncology; May 20-24, 2000; New Orleans, LA; Abstract 1558.
52. Tsuboi M, Ezaki K, Tobinai K, Ohashi Y, Saijo N. Weekly administration of epoetin beta for chemotherapy-induced anemia in cancer patients: results of amulticenter, phase III, randomized, double-blind, placebo-controlled study. Jpn J Clin Oncol. 2009;39(3):163-8.
53. Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, 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.
54. Vadhan-Raj SSJ, Crane C, Buesos-Ramos CE, et al. Randomized, double-blind, placebo-controlled trial of epoetin alfa (Procrit) in patients with rectal and gastric cancer undergoing chemoradiotherapy (CT/RT) followed by surgery: early termination o f the trial due to increased incidence of thrombo-embolic events (TEE). Blood 104:797a. Presented at the 46th Annual Meeting of the American Sociey of Hematology; December 4-7, 2004; San Diego, CA; Abstract 2915.
55. Vansteenkiste J, Pirker R, Massuti B, et al. Double-blind, placebocontrolled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. J N atl Cancer Inst. 2002;94(16):1211-20.
56. Witzig TE, Silberstein PT, Loprinzi CL, et al. Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy. J Clin Oncol. 2005;23(12):2606-17.
57. Wright JR, Ung YC, Julian JA, 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(9):1027-32.
58. Welch RS, James RD, Wilkinson PM, Belli F, Cowan RA. Recombinant human erythropoietin and platinum-based chemotherapy in advanced ovarian cancer. Cancer J Sci Am. 1995;1(4):261-6.
59. Wilkinson PM,Ntonopoulos AM, LahousenM, LindM, Kosmidis P. Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multi-centre, randomised trial. Br J Cancer. 2006;94(7):947-54.
60. Weigang-Köhler K, Vetter A, Thyroff-Friesinger U. HX575, recombinant human epoetin alfa, for the treatment of chemotherapyassociated symptomatic anaemia in patients with solid tumours. Onkologie. 2009;32(4):168-74.
61. Prasad HK, Nelsen D, Siegel ER, Raval G, Rajan S, Hutchins LF. Risk of venous thromboembolism (VTE) in breast cancer patients receiving erythropoietin for chemotherapy-induced anemia: ATertiary Cancer Center experience from the University of Arkansas for Medical Sciences. J Clin Oncol 2008;26:15S. May 20 Supplement; Abstract 20621.
62. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632-4.
63. Hardee ME, Arcasoy MO, Blackwell KL, Kirkpa-trick JP, Dewhirst MW. Erythropoietin biology in cancer. Clin Cancer Res. 2006;12(2):332-9.
64. HardeeME, Rabbani ZN, ArcasoyMO, et al. Erythropoietin inhibits apoptosis in breast cancer cells via an Akt-dependent pathway without modulating in vivo chemosensitivity. Mol Cancer Ther. 2006;5(2):356-61.
65. Acs G, Acs P, Beckwith SM, et al. Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res. 2001;61(9):3561-5.
66. Lai SY, Childs EE, Xi S, et al. Erythropoietin-mediated activation of JAK-STATsignaling contributes to cellular invasion in head and neck squamous cell carcinoma. Oncogene. 2005;24(27):4442-9.
67. Kumar SM, Yu H, FongD, Acs G, Xu X. Erythropoietin activates the phosphoinositide 3-kinase/Akt pathway in human melanoma cells. Melanoma Res. 2006;16(4):275-83.
68. Kumar SM, Acs G, Fang D, Herlyn M, Elder DE, Xu X. Functional erythropoietin autocrine loop in melanoma. Am J Pathol. 2005;166(3):823-30.
69. Lai SY, Grandis J.R. Understanding the presence and function of erythropoietin receptors on cancer cells. J Clin Oncol. 2006;24(29):4675-6.
70. Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;151:419-63.