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Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In add...

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Autores principales: Giampieri, Riccardo, Prete, Michela del, Prochilo, Tiziana, Puzzoni, Marco, Pusceddu, Valeria, Pani, Fabiana, Maccaroni, Elena, Mascia, Roberta, Baleani, Maria Giuditta, Meletani, Tania, Berardi, Rossana, Lanzillo, Anna Maria, Mariotti, Stefano, Zaniboni, Alberto, Cascinu, Stefano, Scartozzi, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380985/
https://www.ncbi.nlm.nih.gov/pubmed/28378839
http://dx.doi.org/10.1038/srep45703
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author Giampieri, Riccardo
Prete, Michela del
Prochilo, Tiziana
Puzzoni, Marco
Pusceddu, Valeria
Pani, Fabiana
Maccaroni, Elena
Mascia, Roberta
Baleani, Maria Giuditta
Meletani, Tania
Berardi, Rossana
Lanzillo, Anna Maria
Mariotti, Stefano
Zaniboni, Alberto
Cascinu, Stefano
Scartozzi, Mario
author_facet Giampieri, Riccardo
Prete, Michela del
Prochilo, Tiziana
Puzzoni, Marco
Pusceddu, Valeria
Pani, Fabiana
Maccaroni, Elena
Mascia, Roberta
Baleani, Maria Giuditta
Meletani, Tania
Berardi, Rossana
Lanzillo, Anna Maria
Mariotti, Stefano
Zaniboni, Alberto
Cascinu, Stefano
Scartozzi, Mario
author_sort Giampieri, Riccardo
collection PubMed
description Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.
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spelling pubmed-53809852017-04-07 Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis Giampieri, Riccardo Prete, Michela del Prochilo, Tiziana Puzzoni, Marco Pusceddu, Valeria Pani, Fabiana Maccaroni, Elena Mascia, Roberta Baleani, Maria Giuditta Meletani, Tania Berardi, Rossana Lanzillo, Anna Maria Mariotti, Stefano Zaniboni, Alberto Cascinu, Stefano Scartozzi, Mario Sci Rep Article Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions. Nature Publishing Group 2017-04-05 /pmc/articles/PMC5380985/ /pubmed/28378839 http://dx.doi.org/10.1038/srep45703 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Giampieri, Riccardo
Prete, Michela del
Prochilo, Tiziana
Puzzoni, Marco
Pusceddu, Valeria
Pani, Fabiana
Maccaroni, Elena
Mascia, Roberta
Baleani, Maria Giuditta
Meletani, Tania
Berardi, Rossana
Lanzillo, Anna Maria
Mariotti, Stefano
Zaniboni, Alberto
Cascinu, Stefano
Scartozzi, Mario
Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title_full Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title_fullStr Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title_full_unstemmed Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title_short Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
title_sort off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: the tribute analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380985/
https://www.ncbi.nlm.nih.gov/pubmed/28378839
http://dx.doi.org/10.1038/srep45703
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