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Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer

BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184...

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Autores principales: Marmorino, Federica, Salvatore, Lisa, Barbara, Cecilia, Allegrini, Giacomo, Antonuzzo, Lorenzo, Masi, Gianluca, Loupakis, Fotios, Borelli, Beatrice, Chiara, Silvana, Banzi, Maria Chiara, Miraglio, Emanuela, Amoroso, Domenico, Dargenio, Francesco, Bonetti, Andrea, Martignetti, Angelo, Paris, Myriam, Tomcikova, Daniela, Boni, Luca, Falcone, Alfredo, Cremolini, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294477/
https://www.ncbi.nlm.nih.gov/pubmed/28081548
http://dx.doi.org/10.1038/bjc.2016.413
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author Marmorino, Federica
Salvatore, Lisa
Barbara, Cecilia
Allegrini, Giacomo
Antonuzzo, Lorenzo
Masi, Gianluca
Loupakis, Fotios
Borelli, Beatrice
Chiara, Silvana
Banzi, Maria Chiara
Miraglio, Emanuela
Amoroso, Domenico
Dargenio, Francesco
Bonetti, Andrea
Martignetti, Angelo
Paris, Myriam
Tomcikova, Daniela
Boni, Luca
Falcone, Alfredo
Cremolini, Chiara
author_facet Marmorino, Federica
Salvatore, Lisa
Barbara, Cecilia
Allegrini, Giacomo
Antonuzzo, Lorenzo
Masi, Gianluca
Loupakis, Fotios
Borelli, Beatrice
Chiara, Silvana
Banzi, Maria Chiara
Miraglio, Emanuela
Amoroso, Domenico
Dargenio, Francesco
Bonetti, Andrea
Martignetti, Angelo
Paris, Myriam
Tomcikova, Daniela
Boni, Luca
Falcone, Alfredo
Cremolini, Chiara
author_sort Marmorino, Federica
collection PubMed
description BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. RESULTS: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23–0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74–1.64)). Consistent results were reported in overall survival (OS; P=0.075). CONCLUSIONS: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.
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spelling pubmed-52944772018-01-31 Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer Marmorino, Federica Salvatore, Lisa Barbara, Cecilia Allegrini, Giacomo Antonuzzo, Lorenzo Masi, Gianluca Loupakis, Fotios Borelli, Beatrice Chiara, Silvana Banzi, Maria Chiara Miraglio, Emanuela Amoroso, Domenico Dargenio, Francesco Bonetti, Andrea Martignetti, Angelo Paris, Myriam Tomcikova, Daniela Boni, Luca Falcone, Alfredo Cremolini, Chiara Br J Cancer Translational Therapeutics BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. RESULTS: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23–0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74–1.64)). Consistent results were reported in overall survival (OS; P=0.075). CONCLUSIONS: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted. Nature Publishing Group 2017-01-31 2017-01-12 /pmc/articles/PMC5294477/ /pubmed/28081548 http://dx.doi.org/10.1038/bjc.2016.413 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Translational Therapeutics
Marmorino, Federica
Salvatore, Lisa
Barbara, Cecilia
Allegrini, Giacomo
Antonuzzo, Lorenzo
Masi, Gianluca
Loupakis, Fotios
Borelli, Beatrice
Chiara, Silvana
Banzi, Maria Chiara
Miraglio, Emanuela
Amoroso, Domenico
Dargenio, Francesco
Bonetti, Andrea
Martignetti, Angelo
Paris, Myriam
Tomcikova, Daniela
Boni, Luca
Falcone, Alfredo
Cremolini, Chiara
Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title_full Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title_fullStr Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title_full_unstemmed Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title_short Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
title_sort serum ldh predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294477/
https://www.ncbi.nlm.nih.gov/pubmed/28081548
http://dx.doi.org/10.1038/bjc.2016.413
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