The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome
Open accessAbstract
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/m2 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/m2 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.
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Cites
Gene Silencing in Cancer in Association with Promoter Hypermethylation
Herman, J. G., & Baylin, S. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023075 · Cited by 3,422
Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
Gottlicher, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.6969 · Cited by 1,887
Histone deacetylases and cancer: causes and therapies
Marks, P. A., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., & Kelly, W. K. (2001) · Nature reviews. Cancer · doi:10.1038/35106079 · Cited by 1,866
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Silverman, L. R., Demakos, E. P., Peterson, B. L., Kornblith, A. B., Holland, J. C., Odchimar-Reissig, R., Stone, R. M., Nelson, D., Powell, B. L., DeCastro, C. M., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.04.117 · Cited by 1,825
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A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
Yang, A. S. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh032 · Cited by 1,033
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Valproic acid hepatic fatalities: A retrospective review
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Histone Deacetylase Inhibitors in Cancer Therapy
Lane, A. A., & Chabner, B. A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.1291 · Cited by 874
Yang, H., Bueso-Ramos, C., DiNardo, C., Estecio, M. R., Davanlou, M., Geng, Q.-R., Fang, Z., Nguyen, M., Pierce, S., Wei, Y., et al. (2014) · Leukemia · doi:10.1038/leu.2013.355 · Cited by 688
Self-citationMolecular and Therapeutic Potential and Toxicity of Valproic Acid
Chateauvieux, S., Morceau, F., Dicato, M., & Diederich, M. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/479364 · Cited by 512
de Lima, M., Giralt, S., Thall, P. F., de Padua Silva, L., Jones, R. B., Komanduri, K., Braun, T. M., Nguyen, H. Q., Champlin, R., & Garcia‐Manero, G. (2010) · Cancer · doi:10.1002/cncr.25500 · Cited by 427
Self-citationNovel histone deacetylase inhibitors in clinical trials as anti-cancer agents
Tan, J., Cang, S., Ma, Y., Petrillo, R. L., & Liu, D. (2010) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-3-5 · Cited by 425
Metadata
- Authors
- Soriano, A. O., Yang, H., Faderl, S., Estrov, Z., Giles, F., Ravandi, F., Cortes, J., Wierda, W. G., Ouzounian, S., Quezada, A., Pierce, S., Estey, E. H., Issa, J.-P. J., Kantarjian, H. M., & Garcia-Manero, G.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-10-01
- Volume
- 110
- Issue
- 7
- Pages
- 2302-2308
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1970772467
- Cited by
- 390
- References
- 32
- FWCI
- 27.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. https://app.cochat.ai/papers/10.1182/blood-2007-03-078576
- The paper
- Soriano, A. O., Yang, H., Faderl, S., Estrov, Z., Giles, F., Ravandi, F., Cortes, J., Wierda, W. G., Ouzounian, S., Quezada, A., Pierce, S., Estey, E. H., Issa, J.-P. J., Kantarjian, H. M., & Garcia-Manero, G. (2007). Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. https://doi.org/10.1182/blood-2007-03-078576
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
