Next Article in Journal
Prognostic Biomarkers in Pancreatic Cancer: Avoiding Errata When Using the TCGA Dataset
Next Article in Special Issue
The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients
Previous Article in Journal
Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Cancers 2019, 11(1), 125; https://doi.org/10.3390/cancers11010125

Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab

1
Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy
2
Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
3
S.C. Farmacie Ospedaliere-Ospedale M.Vittoria-ASL Città di Torino, 10143 Turin, Italy
4
Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, 98125 Messina, Italy
5
Cell Factory Center, University of Messina, 98125 Messina, Italy
6
Department of Experimental Medicine (DiMES), University of Genoa, 16132 Genoa, Italy
7
Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genoa, Italy
8
Immunology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
9
Giannina Gaslini Institute, Via Gerolamo Gaslini, 5, 16147 Genova, Italy
10
Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
11
Division of Clinical Pathology, University Hospital Policlinico G. Martino, 98125 Messina, Italy
12
Interdepartmental Center for Clinical and Experimental Pharmacology (CIFACS), University of Turin, 10149 Turin, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 11 December 2018 / Revised: 12 January 2019 / Accepted: 16 January 2019 / Published: 21 January 2019
Full-Text   |   PDF [1548 KB, uploaded 22 January 2019]   |  

Abstract

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. View Full-Text
Keywords: monoclonal antibody; NSCLC; immunotherapy; ELISA; pharmacokinetics; pharmacogenetics monoclonal antibody; NSCLC; immunotherapy; ELISA; pharmacokinetics; pharmacogenetics
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Cusato, J.; Genova, C.; Tomasello, C.; Carrega, P.; Ottonello, S.; Pietra, G.; Mingari, M.C.; Cossu, I.; Rijavec, E.; Leggieri, A.; Di Perri, G.; Dal Bello, M.G.; Coco, S.; Boccardo, S.; Ferlazzo, G.; Grossi, F.; D’Avolio, A. Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab. Cancers 2019, 11, 125.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top