Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer

BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF),...

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Autores principales: Loupakis, F, Cremolini, C, Fioravanti, A, Orlandi, P, Salvatore, L, Masi, G, Di Desidero, T, Canu, B, Schirripa, M, Frumento, P, Di Paolo, A, Danesi, R, Falcone, A, Bocci, G
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078596/
https://www.ncbi.nlm.nih.gov/pubmed/21407216
http://dx.doi.org/10.1038/bjc.2011.85
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author Loupakis, F
Cremolini, C
Fioravanti, A
Orlandi, P
Salvatore, L
Masi, G
Di Desidero, T
Canu, B
Schirripa, M
Frumento, P
Di Paolo, A
Danesi, R
Falcone, A
Bocci, G
author_facet Loupakis, F
Cremolini, C
Fioravanti, A
Orlandi, P
Salvatore, L
Masi, G
Di Desidero, T
Canu, B
Schirripa, M
Frumento, P
Di Paolo, A
Danesi, R
Falcone, A
Bocci, G
author_sort Loupakis, F
collection PubMed
description BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: −2578A/C, −1498C/T, −1154A/G, −634C/G and 936C/T; and VEGFR-2: −604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients. RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found. CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.
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spelling pubmed-30785962012-04-12 Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer Loupakis, F Cremolini, C Fioravanti, A Orlandi, P Salvatore, L Masi, G Di Desidero, T Canu, B Schirripa, M Frumento, P Di Paolo, A Danesi, R Falcone, A Bocci, G Br J Cancer Clinical Study BACKGROUND: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC). METHODS: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: −2578A/C, −1498C/T, −1154A/G, −634C/G and 936C/T; and VEGFR-2: −604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients. RESULTS: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found. CONCLUSION: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies. Nature Publishing Group 2011-04-12 2011-03-15 /pmc/articles/PMC3078596/ /pubmed/21407216 http://dx.doi.org/10.1038/bjc.2011.85 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical Study
Loupakis, F
Cremolini, C
Fioravanti, A
Orlandi, P
Salvatore, L
Masi, G
Di Desidero, T
Canu, B
Schirripa, M
Frumento, P
Di Paolo, A
Danesi, R
Falcone, A
Bocci, G
Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title_full Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title_fullStr Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title_full_unstemmed Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title_short Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer
title_sort pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line folfoxiri plus bevacizumab schedule in metastatic colorectal cancer
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078596/
https://www.ncbi.nlm.nih.gov/pubmed/21407216
http://dx.doi.org/10.1038/bjc.2011.85
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