Skip to main content
SpringerLink
Log in

Comparison of 7-day azacitidine and 5-day decitabine for treating myelodysplastic syndrome

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Two DNA methyltransferase inhibitors, azacitidine and decitabine, are currently approved for the treatment of myelodysplastic syndrome (MDS). Choosing between these drugs is an important practical issue. In this retrospective study, patients receiving AZA-7d (azacitidine 75 mg/m2 subcutaneously × 7 days, n = 75) or DEC-5d (decitabine 20 mg/m2 intravenously × 5 days, n = 74) were compared. The rates of hematologic response (complete response [CR]/partial response [PR]/marrow CR) were 12.0 % (AZA-7d) vs. 29.7 % (DEC-5d) (P = 0.008), and the overall response rates (CR/PR/marrow CR/hematologic improvement) were 52.0 % (AZA-7d) vs. 63.5 % (DEC-5d) (P = 0.155). Grade 3 or higher neutropenia occurred more frequently with DEC-5d (79.6 %) than with AZA-7d (72.2 %) (P = 0.040). Overall survival probabilities at 2 years were 42.1 % (AZA-7d) vs. 42.2 % (DEC-5d) (P = 0.944). Subgroup analysis revealed that AZA-7d associated with higher survival rates than DEC-5d in patients whose MDS duration exceeded 1 year or who had poor performance status. In conclusion, both AZA-7d and DEC-5d regimens were effective in treating patients with MDS. However, the two regimens differed in terms of clinical responses and toxicities. One hypomethylating regimen may be superior to the other regimen in particular subgroups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425

    Article  PubMed  CAS  Google Scholar 

  2. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10:223–232

    Article  PubMed  CAS  Google Scholar 

  3. Flotho C, Claus R, Batz C, Schneider M, Sandrock I, Ihde S, Plass C, Niemeyer CM, Lubbert M (2009) The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia 23:1019–1028

    Article  PubMed  CAS  Google Scholar 

  4. Gotze K, Platzbecker U, Giagounidis A, Hasse D, Lubbert M, Aul C, Ganser A, Germing U, Hofman WK (2010) Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group. Ann Hematol 89:841

    Article  PubMed  Google Scholar 

  5. Gurion R, Vidal L, Gafter-Gvili A, Belnik Y, Yeshurun M, Raanani P, Shpilberg O (2010) 5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome—a systematic review and meta-analysis. Haematologica 95:303–310

    Article  PubMed  CAS  Google Scholar 

  6. Hagemann S, Heil O, Lyko F, Brueckner B (2011) Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS One 6:e17388

    Article  PubMed  CAS  Google Scholar 

  7. Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C, MacBeth KJ (2010) A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One 5:e9001

    Article  PubMed  Google Scholar 

  8. Hurd PJ, Whitmarsh AJ, Baldwin GS, Kelly SM, Waltho JP, Price NC, Connolly BA, Hornby DP (1999) Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J Mol Biol 286:389–401

    Article  PubMed  CAS  Google Scholar 

  9. Itzykson R, Fenaux P (2012) Predicting the outcome of patients with higher-risk myelodysplastic syndrome treated with hypomethylating agents. Leuk Lymphoma 53:760–762

    Article  PubMed  CAS  Google Scholar 

  10. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H (2006) Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106:1794–1803

    Article  PubMed  CAS  Google Scholar 

  11. Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O’Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP (2007) Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109:52–57

    Article  PubMed  CAS  Google Scholar 

  12. Kumar A, List AF, Hozo I, Komrokji R Djulbegovic B (2010) Decitabine versus 5-azacitidine for the treatment of myelodysplastic syndrome: adjusted indirect meta-analysis. Haematologica 95:340–342, author reply 343–344

    Article  PubMed  Google Scholar 

  13. Lee JH, Jang JH, Park J, Park S, Joo YD, Kim YK, Kim HG, Choi CW, Kim SH, Park SK, Park E, Min YH (2011) A prospective multicenter observational study of decitabine treatment in Korean patients with myelodysplastic syndrome. Haematologica 96:1441–1447

    Article  PubMed  CAS  Google Scholar 

  14. Li LH, Olin EJ, Buskirk HH, Reineke LM (1970) Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia. Cancer Res 30:2760–2769

    PubMed  CAS  Google Scholar 

  15. Lubbert M, Suciu S, Baila L, Ruter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pfluger KH, Coens C, Hagemeijer A, Eckart Schaefer H, Ganser A, Aul C, de Witte T, Wijermans PW (2011) Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol 29:1987–1996

    Article  PubMed  Google Scholar 

  16. Lyko F, Brown R (2005) DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst 97:1498–1506

    Article  PubMed  CAS  Google Scholar 

  17. Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, McIntyre HJ, Fernando IJ, Backstrom JT, Beach CL (2009) Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 27:1850–1856

    Article  PubMed  CAS  Google Scholar 

  18. Marcucci G, Silverman L, Eller M, Lintz L, Beach CL (2005) Bioavailability of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes. J Clin Pharmacol 45:597–602

    Article  PubMed  CAS  Google Scholar 

  19. Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H (2005) Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci U S A 102:8905–8909

    Article  PubMed  CAS  Google Scholar 

  20. Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP (2008) Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood 111:2382–238431

    Article  PubMed  CAS  Google Scholar 

  21. Palii SS, Van Emburgh BO, Sankpal UT, Brown KD, Robertson KD (2008) DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol 28:752–771

    Article  PubMed  CAS  Google Scholar 

  22. Qin T, Jelinek J, Si J, Shu J, Issa JP (2009) Mechanisms of resistance to 5-aza-2'-deoxycytidine in human cancer cell lines. Blood 113:659–667

    Article  PubMed  CAS  Google Scholar 

  23. Qiu X, Hother C, Ralfkiaer UM, Sogaard A, Lu Q, Workman CT, Liang G, Jones PA, Gronbaek K (2010) Equitoxic doses of 5-azacytidine and 5-aza-2'deoxycytidine induce diverse immediate and overlapping heritable changes in the transcriptome. PLoS One 5:pii:e12994

  24. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20:2429–2440

    Article  PubMed  CAS  Google Scholar 

  25. Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL, Larson RA (2006) Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 24:3895–3903

    Article  PubMed  CAS  Google Scholar 

  26. Steensma DP, Baer MR, Slack JL, Buckstein R, Godley LA, Garcia-Manero G, Albitar M, Larsen JS, Arora S, Cullen MT, Kantarjian H (2009) Multicenter study of decitabine administered daily for 5days every 4weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol 27:3842–3848

    Article  PubMed  CAS  Google Scholar 

  27. Steensma DP, Stone RM (2010) Practical recommendations for hypomethylating agent therapy of patients with myelodysplastic syndromes. Hematol Oncol Clin North Am 24:389–406

    Article  PubMed  Google Scholar 

  28. Stresemann C, Lyko F (2008) Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer 123:8–13

    Article  PubMed  CAS  Google Scholar 

  29. Wijermans PW, Krulder JW, Huijgens PC, Neve P (1997) Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia 11:1–5

    Article  PubMed  CAS  Google Scholar 

  30. Wijermans P, Lubbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2000) Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18:956–962

    PubMed  CAS  Google Scholar 

  31. Wijermans PW, Ruter B, Baer MR, Slack JL, Saba HI, Lubbert M (2008) Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res 32:587–591

    Article  PubMed  CAS  Google Scholar 

  32. Yoo CB, Jones PA (2006) Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5:37–50

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A062254).

Conflict of Interest

Je-Hwan Lee has received honoria from Janssen, Korea and Celgene, Korea for lecturing. Other authors have nothing to disclose regarding conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul, 138-736, South Korea

    Je-Hwan Lee, Yunsuk Choi, Sung-Doo Kim, Dae-Young Kim, Jung-Hee Lee & Kyoo-Hyung Lee

  2. Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Sang-Min Lee & Won-Sik Lee

  3. Department of Hematology, Haeundae Paik Hospital, Inje University College of Medicine, 875, Haeun-daero, Haeundae-gu, Busan, 612-862, South Korea

    Su-Hee Cho & Young-Don Joo

Authors
  1. Je-Hwan Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunsuk Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung-Doo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dae-Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jung-Hee Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyoo-Hyung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sang-Min Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Su-Hee Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Won-Sik Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Young-Don Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Je-Hwan Lee or Young-Don Joo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, JH., Choi, Y., Kim, SD. et al. Comparison of 7-day azacitidine and 5-day decitabine for treating myelodysplastic syndrome. Ann Hematol 92, 889–897 (2013). https://doi.org/10.1007/s00277-013-1702-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1702-8

Keywords

Search

Navigation