ArticleInvestigational new drugs2015
A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors.
Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed.
- Dual Targeting EZH2 and Histone Deacetylases in Human Uterine Sarcoma Cells Under Both 2D and 3D Culture Conditions.Journal of cellular and molecular medicine · 2025Article
- Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.Clinical epigenetics · 2025Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Thioredoxin-interacting protein-activated intracellular potassium deprivation mediates the anti-tumour effect of a novel histone acetylation inhibitor HL23, a fangchinoline derivative, in human hepatocellular carcinoma.Journal of advanced research · 2023Article
- Targeting histone deacetylases for cancer therapy: Trends and challenges.Acta pharmaceutica Sinica. B · 2023Review
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- Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives.Cancers · 2021Review
- NCI 6896: a phase I trial of vorinostat (SAHA) and isotretinoin (13-cis retinoic acid) in the treatment of patients with advanced renal cell carcinoma.Investigational new drugs · 2020Article
- Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non-small cell lung cancerOncology letters · 2020Article
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
- Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies.World journal of stem cells · 2019Review
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 2019Review
- Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A.Oncology letters · 2019Article
- Epigenetic Modifications in Thyroid Cancer Cells Restore NIS and Radio-Iodine Uptake and Promote Cell Death.Journal of clinical medicine · 2018Article
- Entinostat reverses P-glycoprotein activation in snail-overexpressing adenocarcinoma HCC827 cells.PloS one · 2018Article
- Epigenetic therapy for the treatment of epithelial ovarian cancer: A clinical review.Gynecologic oncology reports · 2017Review
- Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma.BMC cancer · 2017Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Based on preclinical data demonstrating cytotoxic synergy between sorafenib and entinostat, a phase I study of this combination was conducted in patients with advanced solid tumors. Enrollment followed the traditional "3 + 3" dose escalation scheme. Entinostat was given orally once every 2 weeks, starting at a dose of 4 mg and escalating to 6 and 10 mg every 2 weeks. Sorafenib was administered as a continuous oral dose, escalating from 200 to 400 mg twice daily. A treatment cycle was 28 days. A total of 31 patients with advanced solid tumors were enrolled on the study. The three dose-limiting toxicities (DLTs) observed were grade 3 hand-foot syndrome, nausea/vomiting, and fatigue. MTD was not reached. The recommended phase II dose was defined as the full dose of the respective drugs administered individually. The most common grade 3-4 toxicities were muscle weakness (13 %), skin rash (10 %), fatigue (6 %), diarrhea (6 %), and hand-foot syndrome (3 %). One NSCLC patient achieved a partial response. Two patients (adenocarcinoma of GE junction and Hurthle cell carcinoma of the thyroid) were on the study for more than 9 months with stable disease. The combination of entinostat and sorafenib was well tolerated. Entinostat 10 mg orally once every 2 weeks in combination with sorafenib 400 mg orally twice daily, representing full single agent doses of each drug was identified as the recommended phase 2 dose (RP2D). These data support future clinical development of the combination of entinostat and sorafenib.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.