دورية أكاديمية
Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies
| العنوان: | Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies |
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| المؤلفون: | Morgan, Bruno, Thomas, Anne L., Drevs, Joachim, Hennig, Juergin, Buchert, Martin, Jivan, Asvina, Horsfield, Mark A., Mross, Klauss, Ball, Howard A., Lee, Lucy, Mietlowski, William, Fuxius, Stefan, Unger, Clemens, O'Byrne, Kenneth J., Henry, Andrew, Cherryman, Graham R., Laurent, Dirk, Dugan, Margaret, Marm�, Dieter, Steward, William P. |
| المصدر: | Journal of Clinical Oncology |
| بيانات النشر: | American Society of Clinical Oncology |
| سنة النشر: | 2003 |
| المجموعة: | Queensland University of Technology: QUT ePrints |
| مصطلحات موضوعية: | biological marker, vasculotropin receptor, vatalanib, angiogenesis inhibitor, contrast medium, dichlorobis(ethylenediamine)rhodium(III), organometallic compound, phthalazine derivative, pyridine derivative, angiogenesis, article, clinical article, clinical trial, colorectal cancer, contrast enhancement, controlled clinical trial, controlled study, drug blood level, drug dose escalation, drug mechanism, drug penetration, drug response, human, liver metastasis, nuclear magnetic resonance imaging, phase 1 clinical trial, priority journal, adult, aged, area under the curve |
| الوصف: | Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Morgan, Bruno, Thomas, Anne L., Drevs, Joachim, Hennig, Juergin, Buchert, Martin, Jivan, Asvina, Horsfield, Mark A., Mross, Klauss, Ball, Howard A., Lee, Lucy, Mietlowski, William, Fuxius, Stefan, Unger, Clemens, O'Byrne, Kenneth J., Henry, Andrew, Cherryman, Graham R., Laurent, Dirk, Dugan, Margaret, Marm�, Dieter, & Steward, William P. (2003) Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies. Journal of Clinical Oncology, 21(21), pp. 3955-3964.; https://eprints.qut.edu.au/65227Test/; Faculty of Health; Institute of Health and Biomedical Innovation |
| الإتاحة: | https://doi.org/10.1200/JCO.2003.08.092Test https://eprints.qut.edu.au/65227Test/ |
| حقوق: | © 2003 by American Society of Clinical Oncology. ; This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au |
| رقم الانضمام: | edsbas.50CDDE96 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |