Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial.
Journal
The Lancet. Haematology
ISSN: 2352-3026
Titre abrégé: Lancet Haematol
Pays: England
ID NLM: 101643584
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
29
08
2018
revised:
17
10
2018
accepted:
17
10
2018
pubmed:
14
12
2018
medline:
6
2
2019
entrez:
15
12
2018
Statut:
ppublish
Résumé
Hypomethylating agents, such as decitabine, are the standard of care for older patients with newly diagnosed acute myeloid leukaemia. Single-arm studies have suggested that a 10-day schedule of decitabine cycles leads to better outcomes than the usual 5-day schedule. We compared the efficacy and safety of these two schedules. Eligible patients were aged 60 years or older with acute myeloid leukaemia but unsuitable for intensive chemotherapy (or <60 years if unsuitable for intensive chemotherapy with an anthracycline plus cytarabine). The first 40 patients were allocated equally to the two treatment groups by computer-generated block randomisation (block size 40), after which a response-adaptive randomisation algorithm used all previous patients' treatment and response data to decide the allocation of each following patient favouring the group with superior response. Patients were assigned to receive 20 mg/m Between Feb 28, 2013, and April 12, 2018, 71 patients were enrolled. 28 received decitabine for 5 days and 43 for 10 days, and all were assessable for efficacy and safety. The primary endpoint was achieved in similar proportions of patients in the two treatment groups (12 [43%] of 28 in the 5-day schedule group, 95% credible interval 26-60, and 17 [40%] of 43 in the 10-day schedule group, 26-54, p=0·78; difference 3%, -21 to 27). Total follow-up was 38·2 months, during which the median duration of overall survival was 5·5 months (IQR 2·1-11·7) in the 5-day group and 6·0 months (1·9-11·7) in the 10-day group. 1-year overall survival was 25% in both groups. Complete remission, CRp, CRi, and overall survival did not differ between groups when stratified by cytogenetics, de-novo versus secondary or therapy-related acute myeloid leukaemia, or TP53 In older patients with newly diagnosed acute myeloid leukaemia, efficacy and safety did not differ by the 5-day or the 10-day decitabine schedule. University of Texas MD Anderson Cancer Center and National Cancer Institute Specialized Programs of Research Excellence.
Sections du résumé
BACKGROUND
BACKGROUND
Hypomethylating agents, such as decitabine, are the standard of care for older patients with newly diagnosed acute myeloid leukaemia. Single-arm studies have suggested that a 10-day schedule of decitabine cycles leads to better outcomes than the usual 5-day schedule. We compared the efficacy and safety of these two schedules.
METHODS
METHODS
Eligible patients were aged 60 years or older with acute myeloid leukaemia but unsuitable for intensive chemotherapy (or <60 years if unsuitable for intensive chemotherapy with an anthracycline plus cytarabine). The first 40 patients were allocated equally to the two treatment groups by computer-generated block randomisation (block size 40), after which a response-adaptive randomisation algorithm used all previous patients' treatment and response data to decide the allocation of each following patient favouring the group with superior response. Patients were assigned to receive 20 mg/m
FINDINGS
RESULTS
Between Feb 28, 2013, and April 12, 2018, 71 patients were enrolled. 28 received decitabine for 5 days and 43 for 10 days, and all were assessable for efficacy and safety. The primary endpoint was achieved in similar proportions of patients in the two treatment groups (12 [43%] of 28 in the 5-day schedule group, 95% credible interval 26-60, and 17 [40%] of 43 in the 10-day schedule group, 26-54, p=0·78; difference 3%, -21 to 27). Total follow-up was 38·2 months, during which the median duration of overall survival was 5·5 months (IQR 2·1-11·7) in the 5-day group and 6·0 months (1·9-11·7) in the 10-day group. 1-year overall survival was 25% in both groups. Complete remission, CRp, CRi, and overall survival did not differ between groups when stratified by cytogenetics, de-novo versus secondary or therapy-related acute myeloid leukaemia, or TP53
INTERPRETATION
CONCLUSIONS
In older patients with newly diagnosed acute myeloid leukaemia, efficacy and safety did not differ by the 5-day or the 10-day decitabine schedule.
FUNDING
BACKGROUND
University of Texas MD Anderson Cancer Center and National Cancer Institute Specialized Programs of Research Excellence.
Identifiants
pubmed: 30545576
pii: S2352-3026(18)30182-0
doi: 10.1016/S2352-3026(18)30182-0
pmc: PMC6563344
mid: NIHMS1028847
pii:
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Decitabine
776B62CQ27
Banques de données
ClinicalTrials.gov
['NCT01786343']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29-e37Subventions
Organisme : NCI NIH HHS
ID : K12 CA088084
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Références
Blood. 2004 Mar 1;103(5):1635-40
pubmed: 14604977
J Clin Oncol. 2003 Dec 15;21(24):4642-9
pubmed: 14673054
Cancer. 2006 Mar 1;106(5):1090-8
pubmed: 16435386
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8
pubmed: 20368434
Am J Clin Pathol. 2011 Jan;135(1):35-45
pubmed: 21173122
J Mol Diagn. 2012 Jul;14(4):336-45
pubmed: 22642896
J Clin Oncol. 2012 Jul 20;30(21):2670-7
pubmed: 22689805
Blood. 2012 Dec 6;120(24):4840-5
pubmed: 23071272
Leuk Lymphoma. 2013 Sep;54(9):2003-7
pubmed: 23270581
Haematologica. 2014 Mar;99(3):465-73
pubmed: 24142997
Leuk Lymphoma. 2014 Jul;55(7):1533-7
pubmed: 24144313
Leuk Res. 2014 Jul;38(7):751-5
pubmed: 24836762
J Clin Oncol. 2014 Aug 20;32(24):2541-52
pubmed: 25071138
Blood. 2014 Oct 23;124(17):2705-12
pubmed: 25224413
Nature. 2015 Feb 26;518(7540):552-555
pubmed: 25487151
Blood. 2015 Feb 26;125(9):1367-76
pubmed: 25550361
Blood. 2015 Jul 16;126(3):291-9
pubmed: 25987659
Blood Cancer J. 2015 Jul 31;5:e331
pubmed: 26230955
JAMA. 2015 Aug 25;314(8):811-22
pubmed: 26305651
N Engl J Med. 2015 Sep 17;373(12):1136-52
pubmed: 26376137
Br J Haematol. 2016 Feb;172(3):392-400
pubmed: 26492205
Oncotarget. 2016 Mar 22;7(12):14172-87
pubmed: 26871476
Oncotarget. 2016 Aug 23;7(34):55264-55275
pubmed: 27419369
Cancer. 2016 Nov 15;122(22):3484-3491
pubmed: 27463065
Cancer Discov. 2016 Oct;6(10):1106-1117
pubmed: 27520294
Cancer. 2016 Dec 15;122(24):3821-3830
pubmed: 27529519
Blood Rev. 2017 Mar;31(2):43-62
pubmed: 27745715
N Engl J Med. 2016 Nov 24;375(21):2023-2036
pubmed: 27959731
Cancer. 2017 Oct 1;123(19):3717-3724
pubmed: 28608976
Lancet Oncol. 2018 Feb;19(2):216-228
pubmed: 29339097
N Engl J Med. 2018 Mar 29;378(13):1189-1199
pubmed: 29601269
Blood Adv. 2018 Apr 24;2(8):923-932
pubmed: 29685952
J Clin Oncol. 2018 Jun 20;36(18):1788-1797
pubmed: 29702001