Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome - PubMed (original) (raw)
Clinical Trial
. 2007 Oct 1;110(7):2302-8.
doi: 10.1182/blood-2007-03-078576. Epub 2007 Jun 27.
Hui Yang, Stefan Faderl, Zeev Estrov, Francis Giles, Farhad Ravandi, Jorge Cortes, William G Wierda, Souzanne Ouzounian, Andres Quezada, Sherry Pierce, Elihu H Estey, Jean-Pierre J Issa, Hagop M Kantarjian, Guillermo Garcia-Manero
Affiliations
- PMID: 17596541
- DOI: 10.1182/blood-2007-03-078576
Free article
Clinical Trial
Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome
Andres O Soriano et al. Blood. 2007.
Free article
Abstract
The combination of a DNA hypomethylating agent with a histone deacetylase inhibitor has synergistic antileukemia activity and may restore sensitivity to all-trans retinoic acid (ATRA). We conducted a phase 1/2 study of the combination of 5-azacitidine (5-AZA), valproic acid (VPA), and ATRA in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. 5-AZA was administered subcutaneously at a fixed dose of 75 mg/m(2) daily for 7 days. VPA was dose-escalated and given orally daily for 7 days concomitantly with 5-AZA. ATRA was given at 45 mg/m(2) orally daily for 5 days, starting on day 3. A total of 53 patients were treated. Their median age was 69 years (range, 5-84 years). The maximum tolerated dose of VPA in this combination was 50 mg/kg daily for 7 days. Dose-limiting toxicity was reversible neurotoxicity. The overall response rate was 42%. In previously untreated older patients, the response rate was 52%. Median number of courses to response was 1 (range, 1-3 courses). Median remission duration was 26 weeks, and median survival has not been reached. A significant decrease in global DNA methylation and induction of histone acetylation were achieved. VPA blood levels were higher in responders (P < .005). In conclusion, the combination studied is safe and has significant clinical activity. This clinical trial was registered at www.clinicaltrials.gov as no. NCT00326170.
Similar articles
- Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia.
Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Garcia-Manero G, et al. Blood. 2006 Nov 15;108(10):3271-9. doi: 10.1182/blood-2006-03-009142. Epub 2006 Aug 1. Blood. 2006. PMID: 16882711 Free PMC article. Clinical Trial. - Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome.
Raffoux E, Cras A, Recher C, Boëlle PY, de Labarthe A, Turlure P, Marolleau JP, Reman O, Gardin C, Victor M, Maury S, Rousselot P, Malfuson JV, Maarek O, Daniel MT, Fenaux P, Degos L, Chomienne C, Chevret S, Dombret H. Raffoux E, et al. Oncotarget. 2010 May;1(1):34-42. doi: 10.18632/oncotarget.106. Oncotarget. 2010. PMID: 21293051 Free PMC article. Clinical Trial. - Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia.
Bug G, Ritter M, Wassmann B, Schoch C, Heinzel T, Schwarz K, Romanski A, Kramer OH, Kampfmann M, Hoelzer D, Neubauer A, Ruthardt M, Ottmann OG. Bug G, et al. Cancer. 2005 Dec 15;104(12):2717-25. doi: 10.1002/cncr.21589. Cancer. 2005. PMID: 16294345 Clinical Trial. - The euphoria of hypomethylating agents in MDS and AML: is it justified?
Sekeres MA. Sekeres MA. Best Pract Res Clin Haematol. 2013 Sep;26(3):275-8. doi: 10.1016/j.beha.2013.10.001. Epub 2013 Oct 15. Best Pract Res Clin Haematol. 2013. PMID: 24309530 Review. - Efficacy and Safety of Valproic Acid in Myelodysplastic Syndrome and Acute Myeloid Leukemia; a Narrative Review.
Omidkhoda N, Mahdiani S, Samadi S, Rahimi H, Mohammadpour AH. Omidkhoda N, et al. Drug Res (Stuttg). 2023 Sep;73(7):378-387. doi: 10.1055/a-2088-3718. Epub 2023 May 23. Drug Res (Stuttg). 2023. PMID: 37220791 Review.
Cited by
- Dynamic Regulation of DNA Methylation and Brain Functions.
Xie J, Xie L, Wei H, Li XJ, Lin L. Xie J, et al. Biology (Basel). 2023 Jan 18;12(2):152. doi: 10.3390/biology12020152. Biology (Basel). 2023. PMID: 36829430 Free PMC article. Review. - Histone deacetylase inhibition modulates cell fate decisions during myeloid differentiation.
Bartels M, Geest CR, Bierings M, Buitenhuis M, Coffer PJ. Bartels M, et al. Haematologica. 2010 Jul;95(7):1052-60. doi: 10.3324/haematol.2009.008870. Epub 2010 Jan 27. Haematologica. 2010. PMID: 20107159 Free PMC article. - Is the focus moving toward a combination of targeted drugs?
Grant S. Grant S. Best Pract Res Clin Haematol. 2008 Dec;21(4):629-37. doi: 10.1016/j.beha.2008.08.003. Best Pract Res Clin Haematol. 2008. PMID: 19041602 Free PMC article. Review. - Epigenetic therapy combinations in acute myeloid leukemia: what are the options?
Bewersdorf JP, Shallis R, Stahl M, Zeidan AM. Bewersdorf JP, et al. Ther Adv Hematol. 2019 Jan 11;10:2040620718816698. doi: 10.1177/2040620718816698. eCollection 2019. Ther Adv Hematol. 2019. PMID: 30719265 Free PMC article. Review. - Valproic acid antagonizes the capacity of other histone deacetylase inhibitors to activate the Epstein-barr virus lytic cycle.
Daigle D, Gradoville L, Tuck D, Schulz V, Wang'ondu R, Ye J, Gorres K, Miller G. Daigle D, et al. J Virol. 2011 Jun;85(11):5628-43. doi: 10.1128/JVI.02659-10. Epub 2011 Mar 16. J Virol. 2011. PMID: 21411522 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical