AffiliationCancer Research UK, Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, United Kingdom. Shazza.Rehman@christie-tr.nwest.nhs.uk
MetadataShow full item record
AbstractMany novel antiangiogenic agents are currently in various phases of clinical testing. These agents tend to be cytostatic, and therefore few responses are observed with conventional imaging by computerized tomography. Furthermore, toxicity with these agents is seen when the maximum-tolerated dose is combined with chemotherapy. Hence, there is a need to develop imaging strategies that can determine the minimum and optimum biologically active doses.There is increasing awareness of the need to obtain evidence of drug activity through the use of surrogate markers of the biologic mechanism of action during early clinical trials, in addition to determining the pharmacokinetics, toxicity profile, and maximum-tolerated dose. One of the major impediments to the rapid development of antiangiogenic agents in the past has been the lack of validated assays capable of measuring an antiangiogenic effect directly in patients. Recently, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has emerged as a useful technique for noninvasive imaging of tumor vasculature in preclinical and clinical models.The problem of tumor heterogeneity remains to be addressed. The major challenge is the standardization of the technique worldwide for the purpose of early clinical studies that are likely to be multicenter. Convincing data on correlations between changes observed through molecular imaging and changes in tumor angiogenesis, and hence tumor biology, are still lacking. Whether this would translate into a survival advantage remains to be seen.The ultimate test of the surrogate biological end points determined by molecular imaging will occur in randomized phase III trials. Results of the first randomized trial that showed a survival advantage in favor of antiangiogenic agents were released at the American Society of Clinical Oncology meeting in 2003. There it was reported that the combination of 5-fluorouracil, leucovorin, and irinotecan (Camptosar; Pfizer Pharmaceuticals; New York, NY) with anti-vascular endothelial growth factor antibody (bevacizumab-Avastin; Genentech, Inc.; South San Francisco, CA) was superior to the chemotherapy regimen alone when used to treat patients with metastatic colorectal cancer. However, until further phase III clinical trials confirm these results, surrogate end points of clinical efficacy of the newer agents are urgently needed so that development of ineffective drugs can be halted early. This review briefly discusses the role of molecular imaging in general, and DCE-MRI in particular, in relation to treatment with antiangiogenic agents and highlights some of the difficulties encountered in this area.
CitationMolecular imaging of antiangiogenic agents. 2005, 10 (2):92-103 Oncologist
- [Development of antituberculous drugs: current status and future prospects].
- Authors: Tomioka H, Namba K
- Issue date: 2006 Dec
- Biomarkers for assessment of pharmacologic activity for a vascular endothelial growth factor (VEGF) receptor inhibitor, PTK787/ZK 222584 (PTK/ZK): translation of biological activity in a mouse melanoma metastasis model to phase I studies in patients with advanced colorectal cancer with liver metastases.
- Authors: Lee L, Sharma S, Morgan B, Allegrini P, Schnell C, Brueggen J, Cozens R, Horsfield M, Guenther C, Steward WP, Drevs J, Lebwohl D, Wood J, McSheehy PM
- Issue date: 2006 Jun
- 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.
- Authors: Morgan B, Thomas AL, Drevs J, Hennig J, Buchert M, Jivan A, Horsfield MA, Mross K, Ball HA, Lee L, Mietlowski W, Fuxuis S, Unger C, O'Byrne K, Henry A, Cherryman GR, Laurent D, Dugan M, Marmé D, Steward WP
- Issue date: 2003 Nov 1
- Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker.
- Authors: Hylton N
- Issue date: 2006 Jul 10
- Antivascular cancer treatments: functional assessments by dynamic contrast-enhanced magnetic resonance imaging.
- Authors: Padhani AR, Leach MO
- Issue date: 2005 May-Jun