A Phase I Pharmacokinetic and Pharmacodynamic Study of PX-12, a Novel Inhibitor of Thioredoxin-1, in Patients with Advanced Solid Tumors
| العنوان: | A Phase I Pharmacokinetic and Pharmacodynamic Study of PX-12, a Novel Inhibitor of Thioredoxin-1, in Patients with Advanced Solid Tumors |
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| المؤلفون: | Ramesh K. Ramanathan, Elizabeth R. Sharlow, Catherine A. Cordova, David M. Friedland, Tomislav Dragovich, H-H. Sherry Chow, Steven P. Stratton, Amanda F. Baker, Sylvan B. Green, Chandra P. Belani, D. Lynn Kirkpatrick |
| المصدر: | Clinical Cancer Research. 13:2109-2114 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, Maximum Tolerated Dose, Metabolite, Antineoplastic Agents, Pharmacology, chemistry.chemical_compound, Thioredoxins, Pharmacokinetics, Neoplasms, Humans, Medicine, Disulfides, Aged, Pneumonitis, Aged, 80 and over, Dose-Response Relationship, Drug, business.industry, Imidazoles, Middle Aged, medicine.disease, Vascular endothelial growth factor, Dose–response relationship, Oncology, Tolerability, chemistry, Apoptosis, Area Under Curve, Pharmacodynamics, Female, business |
| الوصف: | Purpose: Thioredoxin-1 (Trx-1) is a cellular redox protein that promotes tumor growth, inhibits apoptosis, and up-regulates hypoxia-inducible factor-1α and vascular endothelial growth factor. Objectives of this study were to determine safety, tolerability, pharmacodynamics, and pharmacokinetics of PX-12, a small-molecule inhibitor of Trx-1. Experimental Design: Thirty-eight patients with advanced solid tumors received PX-12 at doses of 9 to 300 mg/m2, as a 1- or 3-h i.v. infusion on days 1 to 5, repeated every 3 weeks. Results: At the 300 mg/m2 dose level, one patient experienced a reversible episode of pneumonitis during the first cycle, and a second patient developed pneumonitis after the second cycle. Doses up to 226 mg/m2 were well tolerated, and grade 3/4 events were uncommon ( Conclusions: PX-12, the first Trx-1 inhibitor to enter clinical trials, was tolerated up to a dose of 226 mg/m2 by a 3-h infusion. Based on pharmacodynamic and pharmacokinetic data, a trial of prolonged infusion schedule of PX-12 has been initiated. |
| تدمد: | 1557-3265 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fb04dfcd6e01109a4fcc58e9d291d41 https://doi.org/10.1158/1078-0432.ccr-06-2250 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3fb04dfcd6e01109a4fcc58e9d291d41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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