AffiliationAcademic Department of Radiation Oncology and Manchester Molecular Imaging Centre, University of Manchester, Christie NHS Trust Hospital, Wilmslow Road, Manchester M20 4BX, UK.
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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.
CitationCombretastatin A4 phosphate. 2004, 15 (3):179-87 Anticancer Drugs
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- Issue date: 2003 Dec 1
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- Issue date: 2010 Aug
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- Issue date: 2004 Sep
- Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers.
- Authors: Liu YW, De Keyzer F, Feng YB, Chen F, Song SL, Swinnen J, Bormans G, Oyen R, Huang G, Ni YC
- Issue date: 2018 Jul 7
- A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.
- Authors: Abma E, De Spiegelaere W, Vanderperren K, Stock E, Van Brantegem L, Cornelis I, Daminet S, Ni Y, Vynck M, Verstraete G, Smets P, de Rooster H
- Issue date: 2018 Dec