2.50
Hdl Handle:
http://hdl.handle.net/10541/77921
Title:
Combretastatin A4 phosphate.
Authors:
West, Catharine M L; Price, Patricia M
Abstract:
Combretastatin A4 phosphate (CA4P) is a water-soluble prodrug of combretastatin A4 (CA4). The vascular targeting agent CA4 is a microtubule depolymerizing agent. The mechanism of action of the drug is thought to involve the binding of CA4 to tubulin leading to cytoskeletal and then morphological changes in endothelial cells. These changes increase vascular permeability and disrupt tumor blood flow. In experimental tumors, anti-vascular effects are seen within minutes of drug administration and rapidly lead to extensive ischemic necrosis in areas that are often resistant to conventional anti-cancer treatments. Following single-dose administration a viable tumor rim typically remains from which tumor regrowth occurs. When given in combination with therapies targeted at the proliferating viable rim, enhanced tumor responses are seen and in some cases cures. Results from the first clinical trials have shown that CA4P monotherapy is safe and reduces tumor blood flow. There has been some promising demonstration of efficacy. CA4P in combination with cisplatin is also safe. Functional imaging studies have been used to aid the selection of doses for phase II trials. Both dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and positron emission tomography can measure the anti-vascular effects of CA4P in humans. This review describes the background to the development of CA4P, its proposed mechanism of action, the results from the first clinical trials with CA4P and the role of imaging techniques in its clinical development.
Affiliation:
Academic Department of Radiation Oncology and Manchester Molecular Imaging Centre, University of Manchester, Christie NHS Trust Hospital, Wilmslow Road, Manchester M20 4BX, UK.
Citation:
Combretastatin A4 phosphate. 2004, 15 (3):179-87 Anticancer Drugs
Journal:
Anti-Cancer Drugs
Issue Date:
Mar-2004
URI:
http://hdl.handle.net/10541/77921
PubMed ID:
15014350
Type:
Article
Language:
en
ISSN:
0959-4973
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWest, Catharine M L-
dc.contributor.authorPrice, Patricia M-
dc.date.accessioned2009-08-19T15:50:44Z-
dc.date.available2009-08-19T15:50:44Z-
dc.date.issued2004-03-
dc.identifier.citationCombretastatin A4 phosphate. 2004, 15 (3):179-87 Anticancer Drugsen
dc.identifier.issn0959-4973-
dc.identifier.pmid15014350-
dc.identifier.urihttp://hdl.handle.net/10541/77921-
dc.description.abstractCombretastatin A4 phosphate (CA4P) is a water-soluble prodrug of combretastatin A4 (CA4). The vascular targeting agent CA4 is a microtubule depolymerizing agent. The mechanism of action of the drug is thought to involve the binding of CA4 to tubulin leading to cytoskeletal and then morphological changes in endothelial cells. These changes increase vascular permeability and disrupt tumor blood flow. In experimental tumors, anti-vascular effects are seen within minutes of drug administration and rapidly lead to extensive ischemic necrosis in areas that are often resistant to conventional anti-cancer treatments. Following single-dose administration a viable tumor rim typically remains from which tumor regrowth occurs. When given in combination with therapies targeted at the proliferating viable rim, enhanced tumor responses are seen and in some cases cures. Results from the first clinical trials have shown that CA4P monotherapy is safe and reduces tumor blood flow. There has been some promising demonstration of efficacy. CA4P in combination with cisplatin is also safe. Functional imaging studies have been used to aid the selection of doses for phase II trials. Both dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and positron emission tomography can measure the anti-vascular effects of CA4P in humans. This review describes the background to the development of CA4P, its proposed mechanism of action, the results from the first clinical trials with CA4P and the role of imaging techniques in its clinical development.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents, Phytogenic-
dc.subject.meshClinical Trials as Topic-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshStilbenes-
dc.subject.meshTechnology, Pharmaceutical-
dc.titleCombretastatin A4 phosphate.en
dc.typeArticleen
dc.contributor.departmentAcademic Department of Radiation Oncology and Manchester Molecular Imaging Centre, University of Manchester, Christie NHS Trust Hospital, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalAnti-Cancer Drugsen

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