ArticleCancer chemotherapy and pharmacology2021
A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01129193 (Phase I Study of AR-42 in Relapsed Myeloma, Chronic Lymphocytic Leukemia, and Lymphoma), which is not on this map. Cited by 18 papers.
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.
Phase I Study of AR-42 in Relapsed Myeloma, Chronic Lymphocytic Leukemia, and Lymphoma
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Epigenetic Alterations in Meningiomas-A Review.Biomedicines · 2026Review
- Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma.Cell death & disease · 2026Article
- Artificial Intelligence in Computer-Aided Drug Design (CADD) Tools for the Finding of Potent Biologically Active Small Molecules: Traditional to Modern Approach.Combinatorial chemistry & high throughput screening · 2026Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- RNA splicing as a biomarker and phenotypic driver of meningioma DNA-methylation groups.Neuro-oncology · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Targeting histone deacetylase 6 (HDAC6) to enhance radiation therapy in meningiomas in a 2D and 3D in vitro study.EBioMedicine · 2024Article
- New Insights into the LANCL2-Pharmaceutics · 2023Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Review
- Advances in Targeted Therapy for Neurofibromatosis Type 2 (NF2)-Associated Vestibular Schwannomas.Current oncology reports · 2023Review
- Small molecule inhibitors targeting the cancers.MedComm · 2022Review
- Cellular stress modulates severity of the inflammatory response in lungsFrontiers in immunology · 2022Article
- Population Pharmacokinetic Analysis from First-in-Human Data for HDAC Inhibitor, REC-2282 (AR-42), in Patients with Solid Tumors and Hematologic Malignancies: A Case Study for Evaluating Flat vs. Body Size Normalized Dosing.European journal of drug metabolism and pharmacokinetics · 2021Article
- Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.Laryngoscope investigative otolaryngology · 2021Article
- From bench to bedside: Advancing towards therapeutic treatment of vestibular schwannomas.Neuro-oncology advancesReview
- Clinical trials targeting neurofibromatoses-associated tumors: a systematic review.Neuro-oncology advancesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
purposeGiven clinical activity of AR-42, an oral histone deacetylase inhibitor, in hematologic malignancies and preclinical activity in solid tumors, this phase 1 trial investigated the safety and tolerability of AR-42 in patients with advanced solid tumors, including neurofibromatosis type 2-associated meningiomas and schwannomas (NF2). The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives included determining pharmacokinetics and clinical activity.
methodsThis phase I trial was an open-label, single-center, dose-escalation study of single-agent AR-42 in primary central nervous system and advanced solid tumors. The study followed a 3 + 3 design with an expansion cohort at the MTD.
resultsSeventeen patients were enrolled with NF2 (n = 5), urothelial carcinoma (n = 3), breast cancer (n = 2), non-NF2-related meningioma (n = 2), carcinoma of unknown primary (n = 2), small cell lung cancer (n = 1), Sertoli cell carcinoma (n = 1), and uveal melanoma (n = 1). The recommended phase II dose is 60 mg three times weekly, for 3 weeks of a 28-day cycle. DLTs included grade 3 thrombocytopenia and grade 4 psychosis. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. The best response was stable disease in 53% of patients (95% CI 26.6-78.7). Median progression-free survival (PFS) was 3.6 months (95% CI 1.2-9.1). Among evaluable patients with NF2 or meningioma (n = 5), median PFS was 9.1 months (95% CI 1.9-not reached).
conclusionSingle-agent AR-42 is safe and well tolerated. Further studies may consider AR-42 in a larger cohort of patients with NF2 or in combination with other agents in advanced solid tumors.
trial registrationNCT01129193, registered 5/24/2010.
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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.