Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Nivolumab and Vitamin D Concentrations
2.3. Pharmacogenetics
2.4. Regression Analysis
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | n (%), Median (IQR) | |
---|---|---|
n | 45 | |
Age (years) | 73 (65–79.5) | |
Male sex | 31 (69) | |
BMI (Kg/m2) | 23.4 (20.1–26.4) | |
Caucasian | 45 (100) | |
NSCLC type | Adenocarcinoma | 34 (52.3) |
Squamous cell carcinoma | 9 (13.8) | |
Poorly differentiated carcinoma | 1 (1.5) | |
Large-cell neuroendocrine carcinoma | 1 (1.5) | |
Concomitant drugs | Cardiovascular | 24 (36.9) |
Diabetes | 4 (6.2) | |
Opioids | 9 (13.8) | |
Protease inhibitors | 20 (30.8) | |
Corticosteroid | 12 (18.5) | |
Vitamin D | 2 (3.1) | |
Pre-treatment drugs | Cisplatine | 24 (53.3) |
Docetaxel | 10 (22.2) | |
Carboplatine | 24 (53.3) | |
Gemcitabine | 12 (26.7) | |
Gefitinib | 2 (4.4) | |
Pemetrexed | 30 (66.7) | |
Afatinib | 1 (2.2) | |
Osimertinib | 1 (2.2) | |
Erlotinib | 20 (44.4) | |
Vinorelbine | 10 (22.2) | |
Paclitaxel | 3 (6.7) | |
Bevacizumab | 3 (6.7) | |
Etoposide | 4 (8.9) | |
Zoledronic acid | 1 (2.2) | |
Bavicizumab | 1 (2.2) | |
Farletuzumab | 1 (2.2) | |
Radiotherapy | 1 (2.2) |
Single Nucleotide Polymorphism (SNP) | % Homozigous Wild Type | % Heterozygous | % Homozygous Mutant |
---|---|---|---|
CYP27B1 +2838 C > T | 20 CC | 2.2 CT | 77.8 TT |
CYP27B1 −1260 G > T | 73.3 CC | 15.6 CT | 11.1 TT |
CYP24A1 rs2248359 T > C | 42.2 TT | 40 TC | 17.8 CC |
CYP24A1 rs927650 C > T | 33.3 CC | 22.2 CT | 44.5 TT |
CYP24A1 rs2585428 A > G | 31.1 AA | 28.9 AC | 40 CC |
VDR Cdx2 A > G | 17.8 AA | 13.3 AG | 68.9 GG |
VDR TaqI T > C | 33.3 TT | 26.7 TC | 40 CC |
VDR FokI T > C | 11.1 TT | 42.2 TC | 46.7 CC |
VDR BsmI G > A | 42.2 GG | 57.8 GA | - |
VDR ApaI C > A | 26.7 CC | 28.9 CA | 44.4 AA |
VDBP rs7041 T > G | 6.7 TT | 62.2 TG | 31.1 GG |
Variables | Nivolumab Concentrations ≤ 18.7 μg/mL | |||
---|---|---|---|---|
Univariate | Multivariate | |||
p-Value | OR (95% IC) | p-Value | OR (95% IC) | |
BMI < 25 Kg/m2 | 0.766 | 1.270 (0.392–6.112) | ||
Age > 60 years | 0.939 | 0.970 (0.091–9.145) | ||
Gender (male) | 0.213 | 2.260 (0.692–12.419) | ||
Drug dosage < 200 mg | 0.945 | 1.056 (0.099–4.867) | ||
VDBP (GC) AC/CC | 0.059 | 11.667 (0.909–149.700) | 0.049 | 10.667 (0.830–137.145) |
CYP24A1 3999 CC | NC | |||
VDR TaqI TC/CC | 0.164 | 3.077 (0.632–14.976) | ||
CYP27B1 -1260 GG | 0.148 | 3.250 (0.658–16.040) | ||
Pre 25-hydroxyvitamin D levels | NC | NC | ||
Pre 1,25-hydroxyvitamin D levels | 0.124 | 3.840 (0.692–21.312) | ||
Adenocarcinoma NSCLC type | NC | |||
Squamous cell carcinoma | NC | |||
Cisplatine pre-treatment | 0.093 | 4.442 (0.852–24.853) | ||
Carboplatine pre-treatment | 0.190 | 0.300 (0.051–1.854) | ||
Pemetrexed pre-treatment | NC |
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Cusato, J.; Genova, C.; Tomasello, C.; Carrega, P.; Ottonello, S.; Pietra, G.; Mingari, M.C.; Cossu, I.; Rijavec, E.; Leggieri, A.; et al. Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab. Cancers 2019, 11, 125. https://doi.org/10.3390/cancers11010125
Cusato J, Genova C, Tomasello C, Carrega P, Ottonello S, Pietra G, Mingari MC, Cossu I, Rijavec E, Leggieri A, et al. Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab. Cancers. 2019; 11(1):125. https://doi.org/10.3390/cancers11010125
Chicago/Turabian StyleCusato, Jessica, Carlo Genova, Cristina Tomasello, Paolo Carrega, Selene Ottonello, Gabriella Pietra, Maria Cristina Mingari, Irene Cossu, Erika Rijavec, Anna Leggieri, and et al. 2019. "Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab" Cancers 11, no. 1: 125. https://doi.org/10.3390/cancers11010125