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
Open accessAbstract
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 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 2 decitabine intravenously for 5 or 10 consecutive days as induction therapy, every 4-8 weeks for up to three cycles. Responding patients received decitabine as consolidation therapy on a 5-day schedule for up to 24 cycles. We assessed a composite primary endpoint of complete remission, complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete haematological recovery (CRi) achieved at any time and assessed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01786343.Findings 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 mut status. The most common grade 3-4 adverse events were neutropenic fever (seven patients [25%] in the 5-day group and 14 [33%] in the 10-day group) and infection (five [18%] and 16 [37%], respectively). One patient (4%) died from sepsis in the context of neutropenic fever, infection, and haemorrhage in the 5-day group, and in the 10-day group six patients (14%) died from infection. Early mortality was similar in the two groups.Interpretation 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 University of Texas MD Anderson Cancer Center and National Cancer Institute Specialized Programs of Research Excellence.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased HMA duration, such as 10-day decitabine, initially suggested improved outcomes in a limited number of patients with TP53-mutant myeloid malignancies, but there was no improvement in CR or OS in a prospective randomized study comparing 10-day versus 5-day decitabine in AML.
“Increased HMA duration, such as 10-day decitabine, initially suggested improved outcomes in a limited number of patients with TP53-mutant myeloid malignancies (patients with MDS; n = 9),18 but there was no improvement in CR or OS in a prospective randomized study comparing 10-day versus 5-day decitabine in AML, and this treatment schedule has not been widely adopted.19,20”
From Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes (2021) · cites this paper as [19]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Döhner, H., Weisdorf, D. J., & Bloomfield, C. D. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1406184 · Cited by 3,354 · see citing works
Cheson, B. D., Bennett, J. M., Kopecky, K. J., Büchner, T., Willman, C. L., Estey, E. H., Schiffer, C. A., Döhner, H., Tallman, M. S., Lister, T. A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.036 · Cited by 2,686 · see citing works
Creutzig, U., & Kaspers, G. J. L. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.99.116 · Cited by 2,137 · see citing works
Kantarjian, H. M., Thomas, X., Dmoszyńska, A., Wierzbowska, A., Mazur, G. J., Mayer, J., Gau, J., Chou, W., Buckstein, R. J., Čermák, J., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.9429 · Cited by 1,170 · see citing works
Self-citationDombret, H., Seymour, J. F., Butrym, A., Wierzbowska, A., Selleslag, D., Jang, J. H., Kumar, R., Cavenagh, J., Schuh, A. C., Candoni, A., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621664 · Cited by 1,165 · see citing works
Konopleva, M. Y., Pollyea, D. A., Potluri, J., Chyla, B., Hogdal, L. J., Busman, T. A., McKeegan, E. M., Salem, A. H., Zhu, M., Ricker, J. L., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0313 · Cited by 1,067 · see citing works
Self-citationAcute myeloid leukemia ontogeny is defined by distinct somatic mutations
Lindsley, R. C., Mar, B. G., Mazzola, E., Grauman, P. V., Shareef, S., Allen, S. L., Pigneux, A., Wetzler, M., Stuart, R. K., Erba, H. P., et al. (2015) · Blood · doi:10.1182/blood-2014-11-610543 · Cited by 991 · see citing works
Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia
Wong, T. N., Ramsingh, G., Young, A. L., Miller, C. A., Touma, W., Welch, J. S., Lamprecht, T. L., Shen, D., Hundal, J., Fulton, R. S., et al. (2015) · Nature · doi:10.1038/nature13968 · Cited by 892 · see citing works
Issa, J. J., Garcia‐Manero, G., Giles, F. J., Mannari, R. K., Thomas, D. A., Faderl, S. H., Bayar, E., Lyons, J. F., Rosenfeld, C. S., Cortes, J. E., et al. (2003) · Blood · doi:10.1182/blood-2003-03-0687 · Cited by 809 · see citing works
Self-citation<i>TP53</i> and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Welch, J. S., Petti, A. A., Miller, C. A., Fronick, C. C., O’Laughlin, M., Fulton, R. S., Wilson, R. K., Baty, J. D., Duncavage, E. J., Tandon, B., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1605949 · Cited by 796 · see citing works
Molecular Minimal Residual Disease in Acute Myeloid Leukemia
Jongen‐Lavrencic, M., Grob, T., Hanekamp, D., Kavelaars, F. G., Hinai, A. S. A. A., Zeilemaker, A., Erpelinck-Verschueren, C. A. J., Gradowska, P. L., Meijer, R. J., Cloos, J. J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716863 · Cited by 783 · see citing works
Dinardo, C. D., Pratz, K. W., Letai, A. G., Jonas, B. A., Wei, A. H., Thirman, M. J., Arellano, M. L., Frattini, M. G., Kantarjian, H. M., Popovic, R., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30010-x · Cited by 723 · see citing works
Self-citationKantarjian, H. M., O'Brien, S. M., Cortes, J. E., Giles, F. J., Faderl, S. H., Jabbour, E. J., Garcia‐Manero, G., Wierda, W. G., Pierce, S. A., Shan, J., et al. (2006) · Cancer · doi:10.1002/cncr.21723 · Cited by 608 · see citing works
Self-citationTET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients
Bejar, R. L., Lord, A. M., Stevenson, K. E., Bar‐Natan, M., Pérez-Ladaga, A., Zaneveld, J. E., Wang, H., Caughey, B. A., Stojanov, P., Getz, G. A., et al. (2014) · Blood · doi:10.1182/blood-2014-06-582809 · Cited by 563 · see citing works
Self-citationBlum, W. G., Garzon, R., Klisovic, R. B., Schwind, S., Walker, A., Geyer, S. M., Liu, S., Havelange, V., Becker, H., Schaaf, L. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002650107 · Cited by 450 · see citing works
Klco, J. M., Miller, C. A., Griffith, M., Petti, A. A., Spencer, D. H., Ketkar-Kulkarni, S., Wartman, L. D., Christopher, M. J., Westover, T., Helton, N. M., et al. (2015) · JAMA · doi:10.1001/jama.2015.9643 · Cited by 334 · see citing works
Kadia, T. M., Jain, P., Ravandi, F., Garcia‐Manero, G., Andreef, M., Takahashi, K., Borthakur, G. M., Jabbour, E. J., Konopleva, M. Y., Daver, N. G., et al. (2016) · Cancer · doi:10.1002/cncr.30203 · Cited by 261 · see citing works
Self-citationQuintás‐Cardama, A., Ravandi, F., Dumlao, T. L., Brandt, M., Faderl, S., Pierce, S. A., Borthakur, G. M., Garcia‐Manero, G., Cortes, J. E., & Kantarjian, H. M. (2012) · Blood · doi:10.1182/blood-2012-06-436055 · Cited by 218 · see citing works
Self-citationJabbour, E. J., Kantarjian, H. M., O'Brien, S. M., Cortes, J. E., Giles, F. J., Faderl, S. H., Garcia‐Manero, G., Wierda, W. G., Pierce, S. A., Shan, J., et al. (2005) · Blood · doi:10.1182/blood.v106.11.1846.1846 · Cited by 183 · see citing works
Self-citationLuthra, R., Patel, K. P., Reddy, N. G., Haghshenas, V., Routbort, M. J., Harmon, M. A., Barkoh, B. A., Kanagal‐Shamanna, R., Ravandi, F., Cortes, J. E., et al. (2013) · Haematologica · doi:10.3324/haematol.2013.093765 · Cited by 181 · see citing works
Self-citationClearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia
Morita, K., Kantarjian, H. M., Wang, F., Yan, Y., Bueso-Ramos, C., Sasaki, K., Issa, G. C., Wang, S., Jorgensen, J. L., Song, X., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6757 · Cited by 180 · see citing works
Self-citationAcute Myeloid Leukemia With IDH1 or IDH2 Mutation
Patel, K. P., Ravandi, F., Ma, D., Paladugu, A. V., Barkoh, B. A., Medeiros, L. J., & Luthra, R. (2010) · American Journal of Clinical Pathology · doi:10.1309/ajcpd7nr2rmnqdvf · Cited by 177 · see citing works
Self-citationHou, H.-A., Chou, W.-C., Kuo, Y.-Y., Liu, C.-Y., Lin, L., Tseng, M.-H., Chiang, Y.-C., Liu, M.-C., Liu, C.-W., Tang, J.-L., et al. (2015) · Blood Cancer Journal · doi:10.1038/bcj.2015.59 · Cited by 165 · see citing works
Bally, C., Adès, L., Renneville, A., Sebert, M., Eclache, V., Preudhomme, C., Mozziconacci, M.-J., de The, H., Lehmann-Che, J., & Fenaux, P. (2014) · Leukemia Research · doi:10.1016/j.leukres.2014.03.012 · Cited by 162 · see citing works
Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia
Ritchie, E. K., Feldman, E. J., Christos, P. J., Rohan, S. D., Lagassa, C. B., Ippoliti, C. M., Scandura, J. M., Carlson, K.-S., & Roboz, G. J. (2012) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2012.762093 · Cited by 152 · see citing works
Stahl, M. F., DeVeaux, M., Montesinos, P., Itzykson, R., Ritchie, E. K., Sekeres, M. A., Barnard, J., Podoltsev, N. A., Brunner, A. M., Komrokji, R. S., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2018016121 · Cited by 146 · see citing works
Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Adults
Klepin, H. D., Rao, A. V., & Pardee, T. S. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.1564 · Cited by 140 · see citing works
Creutzig, U., Zimmermann, M., Reinhardt, D., Rasche, M., von Neuhoff, C., Alpermann, T., Dworzak, M. N., Perglerová, K., Zemanová, Z., Tchinda, J., et al. (2016) · Cancer · doi:10.1002/cncr.30220 · Cited by 140 · see citing works
Ravandi, F., Jorgensen, J. L., O'Brien, S. M., et al. (2015) · British Journal of Haematology · doi:10.1111/bjh.13834 · Cited by 118 · see citing works
Self-citationTakahashi, K., Patel, K. P., Bueso-Ramos, C., Zhang, J., Gumbs, C. E., Jabbour, E. J., Kadia, T. M., Andreff, M., Konopleva, M. Y., Dinardo, C. D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7290 · Cited by 101 · see citing works
Self-citationSelecting initial treatment of acute myeloid leukaemia in older adults
Podoltsev, N. A., Stahl, M. F., Zeidan, A. M., & Gore, S. D. (2016) · Blood Reviews · doi:10.1016/j.blre.2016.09.005 · Cited by 84 · see citing works
Jung, S., Kim, Y., Yim, S., Kim, H. J., Kwon, Y.-R., Hur, E., Goo, B.-K., Choi, Y., Lee, S. H., Chung, Y., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10526 · Cited by 68 · see citing works
Bhatnagar, B., Duong, V. H., Gourdin, T. S., et al. (2013) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2013.856425 · Cited by 56 · see citing works
Singh, R. R., Bains, A., Patel, K. P., et al. (2012) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2012.02.009 · Cited by 30 · see citing works
Kanagal‐Shamanna, R., Jain, P., Takahashi, K., et al. (2017) · Cancer · doi:10.1002/cncr.30810 · Cited by 24 · see citing works
Self-citationDhulipala, V. C., Extermann, M., Ali, N. E. A., et al. (2016) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2016.07.042 · Cited by 2 · see citing works
Dhulipala, V. C., Extermann, M., Ali, N. E. A., et al. (2015) · Blood · doi:10.1182/blood.v126.23.2505.2505 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes
Sallman, D. A., DeZern, A. E., Garcia-Manero, G., Steensma, D. P., Roboz, G. J., Sekeres, M. A., Cluzeau, T., Sweet, K. L., McLemore, A., McGraw, K. L., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.02341 · Cited by 465 · see citing works
“PRD (63-97) DBD (102-292) TET (323-356) REG (363-393) TAD2 (43-62) TAD1 (1-42) CR mCR + HI mCR HI SD PD NR/NE”
Self-citationCluzeau, T., Sebert, M., Rahmé, R., Cuzzubbo, S., Lehmann-Che, J., Madelaine, I., Peterlin, P., Bève, B., Attalah, H., Chermat, F., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.02342 · Cited by 279 · see citing works
Outcomes of <i>TP53</i>‐mutant acute myeloid leukemia with decitabine and venetoclax
Kim, K., Maiti, A., Loghavi, S., Pourebrahim, R., Kadia, T. M., Rausch, C. R., Furudate, K., Daver, N. G., Alvarado, Y., Ohanian, M., et al. (2021) · Cancer · doi:10.1002/cncr.33689 · Cited by 161 · see citing works
Self-citation
- Authors
- Short, N. J., Kantarjian, H. M., Loghavi, S., Huang, X., Qiao, W., Borthakur, G., Kadia, T. M., Daver, N., Ohanian, M., Dinardo, C. D., Estrov, Z., Kanagal-Shamanna, R., Maiti, A., Benton, C. B., Bose, P., Alvarado, Y., Jabbour, E., Kornblau, S. M., Pemmaraju, N., Jain, N., Gasior, Y., Richie, M. A., Pierce, S., Cortes, J., Konopleva, M., Garcia-Manero, G., & Ravandi, F.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Ravandi, Farhad
- ORCID
- Short, Nicholas J
- Kantarjian, Hagop M
- Loghavi, Sanam
- Huang, Xuelin
- Qiao, Wei
- Borthakur, Gautam
- Kadia, Tapan M
- Daver, Naval
- Ohanian, Maro
- Dinardo, Courtney D
- Estrov, Zeev
- Maiti, Abhishek
- Benton, Christopher B
- Bose, Prithviraj
- Alvarado, Yesid
- Jabbour, Elias
- Kornblau, Steven M
- Pemmaraju, Naveen
- Jain, Nitin
- Pierce, Sherry
- Konopleva, Marina
- Ravandi, Farhad
- Venue
- The Lancet Haematology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 6
- Issue
- 1
- Pages
- e29-e37
- ISSN
- 2352-3026 (ISSN-L)
- PMC
- PMC6563344
- OpenAlex
- W2905325447
- Cited by
- 120
- References
- 37
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 12 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 22 · 2019: 10 · 2018: 1
- FWCI
- 9.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Haematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA016672, K12CA088084)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- decitabine, acute myeloid leukemia, elderly patients, hypomethylating agents, treatment schedule comparison, complete remission, consolidation therapy, induction therapy, overall survival, hematologic toxicity, haematological recovery, frailty index, prognostic factors
- MeSH terms
- Decitabine, Antimetabolites, Antineoplastic, Female, Humans, Male, Middle Aged, Leukemia, Myeloid, Acute, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
