ArticleJournal of clinical pharmacology2016
Effects of UGT1A1 genotype on the pharmacokinetics, pharmacodynamics, and toxicities of belinostat administered by 48-hour continuous infusion in patients with cancer.
Article in Journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors.Pharmaceutical research · 2020Trial
- UGT1A1 genotype-dependent dose adjustment of belinostat in patients with advanced cancers using population pharmacokinetic modeling and simulation.Journal of clinical pharmacology · 2016Trial
- The Dual Role of Human UDP-Glucuronosyltransferase-Mediated Metabolism in Tumor Drug Resistance: Mechanisms and Prospects.International journal of molecular sciences · 2026Review
- Clinical Implications ofPharmaceutics · 2026Review
- Precision Medicine in Non-Hodgkin Lymphoma: Advances in BTK Inhibition, CD30-Directed Antibody-Drug Conjugates, and HDAC-Mediated Epigenetic Therapy with Pirtobrutinib, Brentuximab Vedotin, and Belinostat.Journal of clinical medicine · 2026Review
- Article
- Matrix Approach Assessment of Cabotegravir Drug-Drug Interactions with OAT1/OAT3 Substrates and UGT1A1/UGT1A9 Inhibitors Using Physiologically-Based Pharmacokinetic Modeling.Pharmaceutics · 2025Article
- Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group.Journal of experimental & clinical cancer research : CR · 2023Article
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Defining Clinical Utility of Germline Indicators of Toxicity Risk: A Perspective.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Pharmacogenomics Testing in Phase I Oncology Clinical Trials: Constructive Criticism Is Warranted.Cancers · 2022Review
- Review
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- A population pharmacokinetic/toxicity model for the reduction of platelets during a 48-h continuous intravenous infusion of the histone deacetylase inhibitor belinostat.Cancer chemotherapy and pharmacology · 2018Article
- Uridine 5'-diphospho-glucronosyltrasferase: Its role in pharmacogenomics and human disease.Experimental and therapeutic medicine · 2018Review
- Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung.Anti-cancer drugs · 2018Article
- UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study.Medicine · 2017Observational
- Pharmacogenomics and histone deacetylase inhibitors.Pharmacogenomics · 2016Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The histone deacetylase inhibitor belinostat is eliminated through glucuronidation by UGT1A1. Polymorphisms that reduce UGT1A1 function could result in increased belinostat exposure and toxicities. We wanted to determine which single-nucleotide polymorphisms alter belinostat exposure and toxicity. In a phase 1 trial (belinostat over 48 hours in combination with cisplatin and etoposide), belinostat (400, 500, 600, or 800 mg/m(2) /24 h, 48-hour continuous infusion) was administered to patients with cancer in combination with cisplatin and etoposide (n = 25). Patients were genotyped for UGT1A1 variants associated with reduced function: UGT1A1*6, UGT1A1*28, and UGT1A1*60. End points were associations between UGT1A1 genotype and belinostat pharmacokinetics (PK), toxicities, and global protein lysine acetylation (AcK). Belinostat AUC was increased (P = .003), and t1/2 increased (P = .0009) in UGT1A1*28 and UGT1A1*60 carriers who received more than 400 mg/m(2) /24 h. The incidence of grades 3-4 thrombocytopenia (P = .0081) was associated with UGT1A1 polymorphisms. The US Food and Drug Administration-approved package insert recommends dose adjustment of belinostat for UGT1A1*28. However, our data suggest dose adjustment is also necessary for UGT1A1*60. UGT1A1 polymorphisms were associated with increased systemic belinostat exposure, increased AcK, and increased incidence of toxicities, particularly at doses > 400 mg/m(2) /24 h.
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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.