ArticleBritish journal of cancer2012
Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03829930 (A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer), which is not on this map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Fluid-electrolyte homeostasis requires histone deacetylase function.JCI insight · 2020Pooled it
- Trial
- Immunomodulation by Entinostat in Renal Cell Carcinoma Patients Receiving High-Dose Interleukin 2: A Multicenter, Single-Arm, Phase I/II Trial (NCI-CTEP#7870).Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Targeting Reactive Species Stress and Nutrient Sensing to Enhance NK-Cell Function: Mechanistic Strategies for Overcoming Pancreatic Cancer Progression and Resistance Through Supplement Therapy.International journal of molecular sciences · 2026Review
- Method development and validation for determination of entinostat in human plasma and its application in breast cancer patients.RSC advances · 2026Article
- Decoding the Snail transcriptional network: its role in cancer progression and therapy.Biology direct · 2026Review
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives.RSC advances · 2026Review
- Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma.Cancer research communications · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- 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
- Deregulation of All-International journal of molecular sciences · 2023Review
- Elucidating the direct effects of the novel HDAC inhibitor bocodepsin (OKI-179) on T cells to rationally design regimens for combining with immunotherapy.Frontiers in immunology · 2023Article
- Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?Frontiers in immunology · 2023Review
- What Dietary Patterns and Nutrients are Associated with Pancreatic Cancer? Literature Review.Cancer management and research · 2023Review
- Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir.Scientific reports · 2022Article
- Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy.Journal of gastroenterology · 2022Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPreclinical studies suggest that histone deacetylase (HDAC) inhibitors may restore tumour sensitivity to retinoids. The objective of this study was to determine the safety, tolerability, and the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of the HDAC inhibitor entinostat in combination with 13-cis retinoic acid (CRA) in patients with solid tumours.
methodsPatients with advanced solid tumours were treated with entinostat orally once weekly and with CRA orally twice daily × 3 weeks every 4 weeks. The starting dose for entinostat was 4 mg m(-2) with a fixed dose of CRA at 1 mg kg(-1) per day. Entinostat dose was escalated by 1 mg m(-2) increments. Pharmacokinetic concentrations of entinostat and CRA were determined by LC/MS/MS. Western blot analysis of peripheral blood mononuclear cells and tumour samples were performed to evaluate target inhibition.
resultsA total of 19 patients were enroled. The maximum tolerated dose (MTD) was exceeded at the entinostat 5 mg m(-2) dose level (G3 hyponatremia, neutropenia, and anaemia). Fatigue (G1 or G2) was a common side effect. Entinostat exhibited substantial variability in clearance (147%) and exposure. CRA trough concentrations were consistent with prior reports. No objective responses were observed, however, prolonged stable disease occurred in patients with prostate, pancreatic, and kidney cancer. Data further showed increased tumour histone acetylation and decreased phosphorylated ERK protein expression.
conclusionThe combination of entinostat with CRA was reasonably well tolerated. The recommended phase II doses are entinostat 4 mg m(-2) once weekly and CRA 1 mg kg(-1) per day. Although no tumour responses were seen, further evaluation of this combination is warranted.
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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.