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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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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. |
format | Online Article Text |
id | pubmed-5380985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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