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Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab
Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimin...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357025/ https://www.ncbi.nlm.nih.gov/pubmed/30669662 http://dx.doi.org/10.3390/cancers11010125 |
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author | Cusato, Jessica Genova, Carlo Tomasello, Cristina Carrega, Paolo Ottonello, Selene Pietra, Gabriella Mingari, Maria Cristina Cossu, Irene Rijavec, Erika Leggieri, Anna Di Perri, Giovanni Dal Bello, Maria Giovanna Coco, Simona Boccardo, Simona Ferlazzo, Guido Grossi, Francesco D’Avolio, Antonio |
author_facet | Cusato, Jessica Genova, Carlo Tomasello, Cristina Carrega, Paolo Ottonello, Selene Pietra, Gabriella Mingari, Maria Cristina Cossu, Irene Rijavec, Erika Leggieri, Anna Di Perri, Giovanni Dal Bello, Maria Giovanna Coco, Simona Boccardo, Simona Ferlazzo, Guido Grossi, Francesco D’Avolio, Antonio |
author_sort | Cusato, Jessica |
collection | PubMed |
description | Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in non-small cell lung cancer patients. To date, no data have been reported about the relationship between nivolumab and VD. The aim of this study was to quantify plasma 25-hydroxyVD (25-VD) and 1,25-VD, nivolumab, and its anti-antibody before starting treatment (baseline) and at 15, 45 and 60 days of therapy. VD-pathway-associated gene single nucleotide polymorphisms (SNPs) were also evaluated. Molecules were quantified through enzyme-linked immunosorbent assay, and SNPs through real-time PCR. Forty-five patients were enrolled. Median nivolumab concentrations were 12.5 μg/mL, 22.3 μg/mL and 27.1 μg/mL at 15, 45 and 60 days respectively. No anti-nivolumab antibodies were found. Correlations were observed between nivolumab concentrations and 25-VD levels. Nivolumab concentrations were affected by VD-pathway-related gene SNPs. VDBP AC/CC genotype and baseline 25-VD < 10 ng/mL predicted a nivolumab concentration cut-off value of <18.7 μg/mL at 15 days, which was associated with tumor progression. This is the first study showing VD marker predictors of nivolumab concentrations in a real-life context of non-small cell lung cancer treatment. |
format | Online Article Text |
id | pubmed-6357025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63570252019-02-05 Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab Cusato, Jessica Genova, Carlo Tomasello, Cristina Carrega, Paolo Ottonello, Selene Pietra, Gabriella Mingari, Maria Cristina Cossu, Irene Rijavec, Erika Leggieri, Anna Di Perri, Giovanni Dal Bello, Maria Giovanna Coco, Simona Boccardo, Simona Ferlazzo, Guido Grossi, Francesco D’Avolio, Antonio Cancers (Basel) Article Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in non-small cell lung cancer patients. To date, no data have been reported about the relationship between nivolumab and VD. The aim of this study was to quantify plasma 25-hydroxyVD (25-VD) and 1,25-VD, nivolumab, and its anti-antibody before starting treatment (baseline) and at 15, 45 and 60 days of therapy. VD-pathway-associated gene single nucleotide polymorphisms (SNPs) were also evaluated. Molecules were quantified through enzyme-linked immunosorbent assay, and SNPs through real-time PCR. Forty-five patients were enrolled. Median nivolumab concentrations were 12.5 μg/mL, 22.3 μg/mL and 27.1 μg/mL at 15, 45 and 60 days respectively. No anti-nivolumab antibodies were found. Correlations were observed between nivolumab concentrations and 25-VD levels. Nivolumab concentrations were affected by VD-pathway-related gene SNPs. VDBP AC/CC genotype and baseline 25-VD < 10 ng/mL predicted a nivolumab concentration cut-off value of <18.7 μg/mL at 15 days, which was associated with tumor progression. This is the first study showing VD marker predictors of nivolumab concentrations in a real-life context of non-small cell lung cancer treatment. MDPI 2019-01-21 /pmc/articles/PMC6357025/ /pubmed/30669662 http://dx.doi.org/10.3390/cancers11010125 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cusato, Jessica Genova, Carlo Tomasello, Cristina Carrega, Paolo Ottonello, Selene Pietra, Gabriella Mingari, Maria Cristina Cossu, Irene Rijavec, Erika Leggieri, Anna Di Perri, Giovanni Dal Bello, Maria Giovanna Coco, Simona Boccardo, Simona Ferlazzo, Guido Grossi, Francesco D’Avolio, Antonio Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title | Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title_full | Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title_fullStr | Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title_full_unstemmed | Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title_short | Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab |
title_sort | influence of vitamin d in advanced non-small cell lung cancer patients treated with nivolumab |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357025/ https://www.ncbi.nlm.nih.gov/pubmed/30669662 http://dx.doi.org/10.3390/cancers11010125 |
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