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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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