ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Translational phase I trial of vorinostat (suberoylanilide hydroxamic acid) combined with cytarabine and etoposide in patients with relapsed, refractory, or high-risk acute myeloid leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia.Investigational new drugs · 2015Trial
- Trial
- Treating Relapsed/Refractory Acute Myeloid Leukemia with Chidamide, Fludarabine, Cytarabine and Granulocyte-Colony Stimulating Factor with Subsequent Bridging to Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.Mediterranean journal of hematology and infectious diseases · 2022Article
- Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.BMC cancer · 2021Article
- Epigenetic Regulation of Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein Transporters by Histone Deacetylase Inhibition.Drug metabolism and disposition: the biological fate of chemicals · 2020Review
- Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors.Chinese medical journal · 2020Review
- Brain region-specific regulation of histone acetylation and efflux transporters in mice.Journal of biochemical and molecular toxicology · 2019Article
- Epigenetic therapy combinations in acute myeloid leukemia: what are the options?Therapeutic advances in hematology · 2019Review
- Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.Frontiers in cell and developmental biology · 2019Review
- Tissue-Nonspecific Alkaline Phosphatase Is Required for MC3T3 Osteoblast-Mediated Protection of Acute Myeloid Leukemia Cells from Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- A novel regimen for relapsed/refractory adult acute myeloid leukemia using aHaematologica · 2018Article
- Epigenetic Regulators in the Development, Maintenance, and Therapeutic Targeting of Acute Myeloid Leukemia.Frontiers in oncology · 2018Review
- Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma.Clinical epigenetics · 2018Article
- Histone deacetylase inhibitors reduce differentiating osteoblast-mediated protection of acute myeloid leukemia cells from cytarabine.Oncotarget · 2017Article
- Histone deacetylases 1 and 2 cooperate in regulating BRCA1, CHK1, and RAD51 expression in acute myeloid leukemia cells.Oncotarget · 2017Article
- Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.PloS one · 2017Article
- Chemotherapy Options for Poor Responders to Neoadjuvant Chemotherapy for Orbital Granulocytic Sarcoma.Current treatment options in oncology · 2016Review
- Article
- The targeted histone deacetylase inhibitor tefinostat (CHR-2845) shows selective in vitro efficacy in monocytoid-lineage leukaemias.Oncotarget · 2016Article
- Histone Deacetylase Inhibitors Target the Leukemic Microenvironment by Enhancing a Nherf1-Protein Phosphatase 1α-TAZ Signaling Pathway in Osteoblasts.The Journal of biological chemistry · 2015Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. EXPERIMENTAL
designIn this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m(2)) and cytarabine (1 or 2 g/m(2) twice a day if ≥65 or <65 years old, respectively) were given. The study used a standard 3+3 dose escalation design.
resultsEighteen of 21 patients with acute myelogenous leukemia (AML) treated on study completed planned therapy. Dose-limiting toxicities [hyperbilirubinemia/septic death (1) and anorexia/fatigue (1)] were encountered at the 200 mg three times a day level; thus, the MTD was established to be vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment.
conclusionsVorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings.
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