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Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

BACKGROUND: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. METHODS: In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg), ne...

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Autores principales: Donskov, Frede, Michaelson, M Dror, Puzanov, Igor, Davis, Mellar P, Bjarnason, Georg A, Motzer, Robert J, Goldstein, David, Lin, Xun, Cohen, Darrel P, Wiltshire, Robin, Rini, Brian I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705883/
https://www.ncbi.nlm.nih.gov/pubmed/26492223
http://dx.doi.org/10.1038/bjc.2015.368
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author Donskov, Frede
Michaelson, M Dror
Puzanov, Igor
Davis, Mellar P
Bjarnason, Georg A
Motzer, Robert J
Goldstein, David
Lin, Xun
Cohen, Darrel P
Wiltshire, Robin
Rini, Brian I
author_facet Donskov, Frede
Michaelson, M Dror
Puzanov, Igor
Davis, Mellar P
Bjarnason, Georg A
Motzer, Robert J
Goldstein, David
Lin, Xun
Cohen, Darrel P
Wiltshire, Robin
Rini, Brian I
author_sort Donskov, Frede
collection PubMed
description BACKGROUND: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. METHODS: In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand–foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer PFS (P=0.0276 and P<0.0001, respectively) and OS (P=0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand–foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63−0.67) for IMDC classification alone and 0.72 (95% CI: 0.70−0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). CONCLUSIONS: On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model.
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spelling pubmed-47058832016-01-27 Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients Donskov, Frede Michaelson, M Dror Puzanov, Igor Davis, Mellar P Bjarnason, Georg A Motzer, Robert J Goldstein, David Lin, Xun Cohen, Darrel P Wiltshire, Robin Rini, Brian I Br J Cancer Translational Therapeutics BACKGROUND: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. METHODS: In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand–foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer PFS (P=0.0276 and P<0.0001, respectively) and OS (P=0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand–foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63−0.67) for IMDC classification alone and 0.72 (95% CI: 0.70−0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). CONCLUSIONS: On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model. Nature Publishing Group 2015-12-01 2015-10-22 /pmc/articles/PMC4705883/ /pubmed/26492223 http://dx.doi.org/10.1038/bjc.2015.368 Text en Copyright © 2015 Cancer Research UK http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Translational Therapeutics
Donskov, Frede
Michaelson, M Dror
Puzanov, Igor
Davis, Mellar P
Bjarnason, Georg A
Motzer, Robert J
Goldstein, David
Lin, Xun
Cohen, Darrel P
Wiltshire, Robin
Rini, Brian I
Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title_full Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title_fullStr Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title_full_unstemmed Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title_short Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
title_sort sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705883/
https://www.ncbi.nlm.nih.gov/pubmed/26492223
http://dx.doi.org/10.1038/bjc.2015.368
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