Literature DB >> 21656747

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes.

Lewis R Silverman1, Pierre Fenaux, Ghulam J Mufti, Valeria Santini, Eva Hellström-Lindberg, Norbert Gattermann, Guillermo Sanz, Alan F List, Steven D Gore, John F Seymour.   

Abstract

BACKGROUND: In the AZA-001 trial, azacitidine (75 mg/m(2) /d subcutaneously for Days 1-7 of every 28-day cycle) demonstrated improved survival compared with conventional care regimens in patients with International Prognostic Scoring System-defined intermediate-2- or high-risk myelodysplastic syndrome and World Health Organization-defined acute myeloid leukemia with 20% to 30% bone marrow blasts.
METHODS: This secondary analysis of the AZA-001 phase 3 study evaluated the time to first response and the potential benefit of continued azacitidine treatment beyond first response in responders.
RESULTS: Overall, 91 of 179 patients achieved a response to azacitidine; responding patients received a median of 14 treatment cycles (range, 2-30). Median time to first response was 2 cycles (range, 1-16). Although 91% of first responses occurred by 6 cycles, continued azacitidine improved response category in 48% of patients. Best response was achieved by 92% of responders by 12 cycles. Median time from first response to best response was 3.5 cycles (95% confidence interval [CI], 3.0-6.0) in 30 patients who ultimately achieved a complete response, and 3.0 cycles (95% CI, 1.0-3.0) in 21 patients who achieved a partial response.
CONCLUSIONS: Continued azacitidine therapy in responders was associated with a quantitative increase in response to a higher response category in 48% of patients, and therefore may enhance clinical benefit in patients with higher-risk MDS.
Copyright © 2011 American Cancer Society.

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Year:  2011        PMID: 21656747      PMCID: PMC4000012          DOI: 10.1002/cncr.25774

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  17 in total

1.  Report of an international working group to standardize response criteria for myelodysplastic syndromes.

Authors:  B D Cheson; J M Bennett; H Kantarjian; A Pinto; C A Schiffer; S D Nimer; B Löwenberg; M Beran; T M de Witte; R M Stone; M Mittelman; G F Sanz; P W Wijermans; S Gore; P L Greenberg
Journal:  Blood       Date:  2000-12-01       Impact factor: 22.113

Review 2.  Gene silencing in cancer in association with promoter hypermethylation.

Authors:  James G Herman; Stephen B Baylin
Journal:  N Engl J Med       Date:  2003-11-20       Impact factor: 91.245

3.  Improving survival in myelodysplastic syndromes.

Authors:  Guillermo Garcia-Manero
Journal:  Lancet Oncol       Date:  2009-03       Impact factor: 41.316

Review 4.  Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine.

Authors:  Carlo Stresemann; Frank Lyko
Journal:  Int J Cancer       Date:  2008-07-01       Impact factor: 7.396

5.  Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B.

Authors:  Lewis R Silverman; David R McKenzie; Bercedis L Peterson; James F Holland; Jay T Backstrom; C L Beach; Richard A Larson
Journal:  J Clin Oncol       Date:  2006-08-20       Impact factor: 44.544

6.  Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B.

Authors:  Lewis R Silverman; Erin P Demakos; Bercedis L Peterson; Alice B Kornblith; Jimmie C Holland; Rosalie Odchimar-Reissig; Richard M Stone; Douglas Nelson; Bayard L Powell; Carlos M DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; James F Holland
Journal:  J Clin Oncol       Date:  2002-05-15       Impact factor: 44.544

7.  Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study.

Authors:  Alice B Kornblith; James E Herndon; Lewis R Silverman; Erin P Demakos; Rosalie Odchimar-Reissig; James F Holland; Bayard L Powell; Carlos DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; Jimmie C Holland
Journal:  J Clin Oncol       Date:  2002-05-15       Impact factor: 44.544

Review 8.  Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications.

Authors:  V Santini; H M Kantarjian; J P Issa
Journal:  Ann Intern Med       Date:  2001-04-03       Impact factor: 25.391

9.  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.

Authors:  Pierre Fenaux; Ghulam J Mufti; Eva Hellstrom-Lindberg; Valeria Santini; Carlo Finelli; Aristoteles Giagounidis; Robert Schoch; Norbert Gattermann; Guillermo Sanz; Alan List; Steven D Gore; John F Seymour; John M Bennett; John Byrd; Jay Backstrom; Linda Zimmerman; David McKenzie; Cl Beach; Lewis R Silverman
Journal:  Lancet Oncol       Date:  2009-02-21       Impact factor: 41.316

Review 10.  Allogeneic stem cell transplantation for myelodysplastic syndrome.

Authors:  A John Barrett; Bipin N Savani
Journal:  Semin Hematol       Date:  2008-01       Impact factor: 3.851

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  57 in total

Review 1.  New ways to use DNA methyltransferase inhibitors for the treatment of myelodysplastic syndrome.

Authors:  Steven D Gore
Journal:  Hematology Am Soc Hematol Educ Program       Date:  2011

2.  Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: results from the Dutch population-based PHAROS MDS registry.

Authors:  A G Dinmohamed; Y van Norden; O Visser; E F M Posthuma; P C Huijgens; P Sonneveld; A A van de Loosdrecht; M Jongen-Lavrencic
Journal:  Leukemia       Date:  2015-09-15       Impact factor: 11.528

Review 3.  Why methylation is not a marker predictive of response to hypomethylating agents.

Authors:  Maria Teresa Voso; Valeria Santini; Emiliano Fabiani; Luana Fianchi; Marianna Criscuolo; Giulia Falconi; Francesco Guidi; Stefan Hohaus; Giuseppe Leone
Journal:  Haematologica       Date:  2014-04       Impact factor: 9.941

Review 4.  DNA Hypomethylating Drugs in Cancer Therapy.

Authors:  Takahiro Sato; Jean-Pierre J Issa; Patricia Kropf
Journal:  Cold Spring Harb Perspect Med       Date:  2017-05-01       Impact factor: 6.915

5.  Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study.

Authors:  Amy J Davidoff; Xin Hu; Jan Philipp Bewersdorf; Rong Wang; Nikolai A Podoltsev; Scott F Huntington; Steven D Gore; Xiaomei Ma; Amer M Zeidan
Journal:  Leuk Lymphoma       Date:  2019-12-26

6.  Obstacles to adherence to azacitidine administration schedule in outpatient myelodysplastic syndrome and related disorders.

Authors:  Andrea Tendas; Maria Felicita Lissia; Daniela Piccioni; Liliana Tirimbelli; Laura Scaramucci; Marco Giovannini; Teresa Dentamaro; Alessio Perrotti; Paolo de Fabritiis; Pasquale Niscola
Journal:  Support Care Cancer       Date:  2014-11-05       Impact factor: 3.603

Review 7.  The future of epigenetic therapy in solid tumours--lessons from the past.

Authors:  Nilofer Azad; Cynthia A Zahnow; Charles M Rudin; Stephen B Baylin
Journal:  Nat Rev Clin Oncol       Date:  2013-04-02       Impact factor: 66.675

8.  Optimizing outcomes with azacitidine: recommendations from Canadian centres of excellence.

Authors:  R A Wells; B Leber; N Y Zhu; J M Storring
Journal:  Curr Oncol       Date:  2014-02       Impact factor: 3.677

Review 9.  Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia.

Authors:  Lesley J Scott
Journal:  Drugs       Date:  2016-05       Impact factor: 9.546

10.  Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

Authors:  Rami Komrokji; Arlene S Swern; David Grinblatt; Roger M Lyons; Magnus Tobiasson; Lewis R Silverman; Hamid Sayar; Ravi Vij; Albert Fliss; Nora Tu; Mary M Sugrue
Journal:  Oncologist       Date:  2017-11-08
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