ArticleCancer chemotherapy and pharmacology2015
A phase I, pharmacokinetic, and pharmacodynamic evaluation of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine, administered with tetrahydrouridine.
Article in Cancer chemotherapy and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review.Drug design, development and therapy · 2015Pooled it
- Clinicopathological significance and potential drug target of CDH1 in breast cancer: a meta-analysis and literature review.Drug design, development and therapy · 2015Pooled it
- Intravenous 5-fluoro-2'-deoxycytidine administered with tetrahydrouridine increases the proportion of p16-expressing circulating tumor cells in patients with advanced solid tumors.Cancer chemotherapy and pharmacology · 2020Trial
- Biodistribution, Tumor Detection, and Radiation Dosimetry ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Trial
- Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans.Cancer chemotherapy and pharmacology · 2015Trial
- Host-Pathogen Dual Targeting With Repurposed Drugs Identifies a Synergistic Therapy for Intracellular Staphylococcus aureus.MicrobiologyOpen · 2026Article
- A phase 1 study of orally administered 5-fluoro-2'-deoxycytidine with tetrahydrouridine in patients with refractory solid tumors.Cancer chemotherapy and pharmacology · 2025Article
- Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.Discover oncology · 2024Review
- Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance.Nature cancer · 2024Article
- Review
- Combined inhibition of histone deacetylase and cytidine deaminase improves epigenetic potency of decitabine in colorectal adenocarcinomas.Clinical epigenetics · 2023Article
- The potential regulatory role of RNA methylation in ovarian cancer.RNA biology · 2023Review
- Functional Drug Screening of Small Molecule Inhibitors of Epigenetic Modifiers in Refractory AML Patients.Cancers · 2022Article
- Recent progress in DNA methyltransferase inhibitors as anticancer agents.Frontiers in pharmacology · 2022Review
- Ultrasensitive DNA methyltransferase activity sensing and inhibitor evaluation with highly photostable upconversion nanoparticle transducer.Mikrochimica acta · 2021Article
- Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.Journal of biomedical science · 2021Review
- Comprehensive analysis of regulation of DNA methyltransferase isoforms in human breast tumors.Journal of cancer research and clinical oncology · 2021Review
- Decitabine mildly attenuatesEJHaem · 2020Article
- Review
- Clinicopathological and prognostic significance ofCancer management and research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 1 country.
Funding
Abstract
purposeInhibitors of DNA (cytosine-5)-methyltransferases (DNMT) are active antineoplastic agents. We conducted the first-in-human phase I trial of 5-fluoro-2'-deoxycytidine (FdCyd), a DNMT inhibitor stable in aqueous solution, in patients with advanced solid tumors. Objectives were to establish the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of FdCyd + tetrahydrouridine (THU).
methodsFdCyd + THU were administered by 3 h IV infusion on days 1-5 every 3 weeks, or days 1-5 and 8-12 every 4 weeks. FdCyd was administered IV with a fixed 350 mg/m(2)/day dose of THU to inhibit deamination of FdCyd. Pharmacokinetics of FdCyd, downstream metabolites and THU were assessed by LC-MS/MS. RBC γ-globin expression was evaluated as a pharmacodynamics biomarker.
resultsPatients were enrolled on the 3-week schedule at doses up to 80 mg/m(2)/day without dose-limiting toxicity (DLT) prior to transitioning to the 4-week schedule, which resulted in an MTD of 134 mg/m(2)/day; one of six patients had a first-cycle DLT (grade 3 colitis). FdCyd ≥40 mg/m(2)/day produced peak plasma concentrations >1 µM. Although there was inter-patient variability, γ-globin mRNA increased during the first two treatment cycles. One refractory breast cancer patient experienced a partial response (PR) of >90 % decrease in tumor size, lasting over a year.
conclusionsThe MTD was established at 134 mg/m(2) FdCyd + 350 mg/m(2) THU days 1-5 and 8-12 every 4 weeks. Based on toxicities observed over multiple cycles, good plasma exposures, and the sustained PR observed at 67 mg/m(2)/day, the phase II dose for our ongoing multi-histology trial is 100 mg/m(2)/day FdCyd with 350 mg/m(2)/day THU.
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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.