Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the randomised CONFIRM trials
Autor: | D Laurent, M I Koukourakis, M. Shi, David Lebwohl, Adrian L. Harris, Gerold Meinhardt, Alexandra Giatromanolaki, Gunnar Folprecht, Efthimios Sivridis, Tanja Trarbach, K C Gatter, T Jalava |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Oncology
Adult Male Cancer Research Pathology medicine.medical_specialty Vatalanib Disease free survival Colorectal cancer Pyridines Medizin Angiogenesis Inhibitors colorectal cancer Disease-Free Survival Predictive Value of Tests KDR Internal medicine medicine Humans Aged Aged 80 and over Neovascularization Pathologic business.industry Disease progression Endothelial Cells Kinase insert domain receptor Middle Aged medicine.disease Prognosis Immunohistochemistry Vascular Endothelial Growth Factor Receptor-2 Platelet Endothelial Cell Adhesion Molecule-1 VEGFR2 Predictive value of tests Density analysis Disease Progression Clinical Study Phthalazines vatalanib Female CONFIRM CD31 business Colorectal Neoplasms |
Zdroj: | British Journal of Cancer |
DOI: | 10.1038/bjc.2012.369 |
Popis: | Background: Pharmacological inhibitors of vascular endothelial growth factor (VEGF) receptors, like vatalanib, have been tested in randomised trials (CONFIRM (Colorectal Oral Novel therapy For the Inhibition of Angiogenesis and Retarding of Metastases) 1 and 2) in colorectal cancer showing activity in a subgroup of patients with high serum LDH expression. In the current study, we assessed the predictive role of vascular density (VD) in patients treated in the above trials. Methods: Paraffin-embedded materials from 141 patients were analysed with immunohistochemistry for the expression of the CD31 (pan-endothelial cell marker) and of phosphorylated pVEGFR2/KDR on endothelial cells. The VD was correlated with response to therapy and with progression-free (PFS) and overall survival (OS). Results: A significant association of pVEGFR2/KDR VD with poor response in the placebo group was noted (response rates (RRs) 15% (3/20) when high VD vs 52% (26/50) when low VD; P=0.006). The RR increased from 15 (3/20) to 50% (11/22) in tumours with high VD when vatalanib was added to chemotherapy (P=0.02). A significantly improved PFS was noted in patients with high pVEGFR2/KDR VD when treated with vatalanib (P=0.002). A similar effect was also noted in patients with high CD31 VD (P=0.07). Overall survival was marginally improved (P=0.07).Conclusion:Assessment of the activated vessel density may allow the stratification of patients recruited in randomised trials with VEGFR-targeting anti-angiogenic agents, unmasking their therapeutic potential and enabling their introduction in the clinical practice for the benefit of specific patient subgroups, at the same time reducing the cost of therapy. © 2012 Cancer Research UK All rights reserved. |
Databáze: | OpenAIRE |
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