Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.

1.
Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, Carraway H, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Horsfall R, Johnson RA, Juckett M, Klimek VM, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Shami PJ, Stein BL, Walker AR, Westervelt P, Zeidan A, Shead DA, Smith C: Myelodysplastic syndromes, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 2017;15:60-87.
2.
Ma X, Does M, Raza A, Mayne ST: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 2007;109:1536-1542.
3.
Kantarjian H, Issa JP, Rosenfeld CS, Mayne ST: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794-1803.
4.
Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pflüger KH, Coens C, Hagemeijer A, Eckart Schaefer H, Ganser A, Aul C, de Witte T, Wijermans PW: 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 2011;29:1987-1996.
5.
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: Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:52-57.
6.
Steensma DP, Baer MR, Slack JL, Buckstein R, Godley LA, Garcia-Manero G, Albitar M, Larsen JS, Arora S, Cullen MT, Kantarjian H: Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol 2009;27:3842-3848.
7.
Wu D, Du X, Jin J , Xiao Z, Shen Z, Shao Z , Li X, Huang X, Liu T, Yu L, Li J, Chen B, He G, Cai Z, Liang H, Li J, Ruan C: Decitabine for treatment of myelodysplastic syndromes in Chinese patients: an open-label, phase-3b study. Adv Ther 2015;32:1140-1159.
8.
Wang R, Gross CP, Frick K, Xu X, Long J, Raza A, Galili N, Zikria J, Guan Y, Ma X: The Impact of hypomethylating agents on the cost of care and survival of elderly patients with myelodysplastic syndromes. Leuk Re 2012;36:1370-1375.
9.
Kantarjian H, O'Brien S, Ravandi F, Cortes J, Shan J, Bennett JM, List A, Fenaux P, Sanz G, Issa JP, Freireich EJ, Garcia-Manero G: Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 2008;113:1351-1361.
10.
Issa J-P, Garcia-Manero G, Giles FJ. Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM: Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004;103:1635-1640.
11.
Garcia-Manero G, Jabbour E, Borthakur G, Faderl S, Estrov Z, Yang H, Maddipoti S, Godley LA, Gabrail N, Berdeja JG, Nadeem A, Kassalow L, Kantarjian H: Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes. J Clin Oncol 2013;31:2548-2553.
12.
Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B: Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol 2011;29:2521-2527.
13.
Jie L, Hongli Z, Suxia L, Hui F, Xuechun L, Cheng C, Guo B, Zhai B: Successful treatment with low-dose decitabine in acute myelogenous leukemia in elderly patients over 80 years old: five case reports. Oncol Lett 2013;5:1321-1324.
14.
Li X, Song Q, Chen Y, Chang C, Wu D, Wu L, Su J, Zhang X, Zhou L, Song L, Zhang Z, Xu F, Hou M: Decitabine of reduced dosage in Chinese patients with myelodysplastic syndrome: a retrospective analysis. PLoS One 2014;9:e95473.
15.
Nie J, Zhang Y, Li X, Chen M,,Liu C, Han W. DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. Oncotarget 2016;7:37882-37892.
16.
Wang L, Amoozgar Z, Huang J, Saleh MH, Xing D, Orsulic S, Goldberg MS: Decitabine enhances lymphocyte migration and function and synergizes with CTLA-4 blockade in a murine ovarian cancer model. Cancer Immunol Res 2015;3:1030-1041.
17.
Wang H, Yang B, Chi X, Cai L, Yu R, Zhu H, Tuo S, Zhang F, Wang X, Yang Y, Wu X, Li S, Lu X: Ultra-low-dose decitabine combined with autologous cytokine-induced killer cells for elderly patients with acute myeloid leukemia transformed from myelodysplastic syndrome. Clin Ther 2014;36:1104-1111.
18.
Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon B, Lee YS, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ: TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes, N Engl J Med 2016;375:2023-2036.
19.
Wu L, Li X, Chang C, Xu F, He Q, Wu D, Zhang Z, Su J, Zhou L, Song L, Chao X, Zhao Y: Efficacy and toxicity of decitabine versus CHG regimen (low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor) in patients with higher risk myelodysplastic syndrome: a retrospective study. Leuk Lymphoma 2016;57:1367-1374.
20.
Chang CK, Zhao YS, Xu F, Guo J, Zhang Z, He Q, Wu D, Wu LY, Su JY, Song LX, Xiao C, Li X: TP53 mutations predict decitabine-induced complete responses in patients with myelodysplasticsyndromes.Br J Haematol 2017;176:600-608.
21.
Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J, Wang H, Caughey B, Stojanov P, Getz G, Garcia-Manero G, Kantarjian H, Chen R, Stone RM, Neuberg D, Steensma DP, Ebert BL: ET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014;124:2705-2712.
22.
Cabrero M, Jabbour E, Ravandi F, Bohannan Z, Pierce S, Kantarjian HM, Garcia-Manero G: Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up. Leuk Res 2015;39:520-524.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.