ArticleInvestigational new drugs2007
A phase 1 trial of XK469: toxicity profile of a selective topoisomerase IIbeta inhibitor.
Article in Investigational new drugs, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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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
11 citing papers in PubMed.
- Design, Synthesis of Pyridine Based Thiazolidine Derivatives and Investigation of Antimicrobial Activity Targeting Ergosterol Biosynthesis via In Vitro and In Silico Approaches.Chemical biology & drug design · 2026Article
- Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2024Article
- Use of CRISPR/Cas9 with Homology-Directed Repair to Gene-Edit Topoisomerase IIThe Journal of pharmacology and experimental therapeutics · 2024Article
- Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Effects of hsa-miR-9-3p and hsa-miR-9-5p on Topoisomerase IIThe Journal of pharmacology and experimental therapeutics · 2023Article
- Synthesis, In Vitro Antiproliferative Activity, and In Silico Evaluation of Novel Oxiranyl-Quinoxaline Derivatives.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Quinoxaline 1,4-di-N-Oxides: Biological Activities and Mechanisms of Actions.Frontiers in pharmacology · 2016Review
- Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes.Nanomedicine : nanotechnology, biology, and medicine · 2013Article
- Multiple peaking phenomena in pharmacokinetic disposition.Clinical pharmacokinetics · 2010Review
- Theoretical and practical application of traditional and accelerated titration Phase I clinical trial designs: the Wayne State University experience.Journal of biopharmaceutical statistics · 2009Article
- A phase I and pharmacokinetic study of the quinoxaline antitumour Agent R(+)XK469 in patients with advanced solid tumours.European journal of cancer (Oxford, England : 1990) · 2008Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
purposeXK469, a member of the quinoxaline family of antitumor agents, is believed to be unique in its ability to selectively target topoisomerase IIbeta. Based on encouraging pre-clinical data, a phase I trial was conducted to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD).
methodsA 2B accelerated titration schema was employed. XK469 was administered as a 5 or 20 min IV infusion on days 1-5 every 21 days. The starting dose was 9 mg/m(2). Pharmacokinetics (PK) were conducted in cycles 1-3.
results22 patients (21 evaluable, mean age: 56 years, median performance status: 1) were enrolled. At dose level 11 (260 mg/m(2)/daily X 5), 1/6 patients experienced a DLT of grade 4 neutropenia. At 346 mg/m(2)/daily X 5, 2/2 patients experienced DLT's with one episode of febrile neutropenia and one grade 3 infection. The MTD was identified as 260 mg/m(2)/day. XK469 peak plasma levels and systemic exposure were proportional to dose indicating linear pharmacokinetics. However, secondary peaks in the PK profiles and a rapid decline in drug level from 23 to 24 h occurred in some patients. Drug infusion in the afternoon followed by dense sampling of levels during the elimination phase supported the hypothesis that the drug was being sequestered. No anti-tumor activity was identified.
conclusionsTraditional PK sampling designs were inadequate to describe XK469 disposition. XK469 and related structures work through a unique mechanism of action. A further understanding of the specific mechanism of these compounds might uncover a unique avenue for future drug development.
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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.