Reproducibility of pharmacogenetics findings for paclitaxel in a heterogeneous population of patients with lung cancer.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
01
2018
accepted:
28
01
2019
entrez:
1
3
2019
pubmed:
1
3
2019
medline:
12
11
2019
Statut:
epublish
Résumé
Pharmacogenetics studies have identified several allelic variants with the potential to reduce toxicity and improve treatment outcome. The present study was designed to determine if such findings are reproducible in a heterogenous population of patients with lung cancer undergoing therapy with paclitaxel. We designed a prospective multi-institutional study that recruited n = 103 patients receiving paclitaxel therapy with a 5-year follow up. All patients were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) platform, which ascertains 1931 genotypes in 235 genes. Progression-free survival (PFS) of paclitaxel therapy and clinically-significant paclitaxel toxicities were classified and compared according to genotype. Initial screening revealed eleven variants that are associated with PFS. Of these, seven variants in ABCB11 (rs4148768), ABCC3 (rs1051640), ABCG1 (rs1541290), CYP8B1 (rs735320), NR3C1 (rs6169), FMO6P (rs7889839), and GSTM3 (rs7483) were associated with paclitaxel PFS in a multivariate analysis accounting for clinical covariates. Multivariate analysis revealed four SNPs in VKORC1 (rs2884737), SLC22A14 (rs4679028), GSTA2 (rs6577), and DCK (rs4643786) were associated with paclitaxel toxicities. With the exception of a variant in VKORC1, the present study did not find the same genetic outcome associations of other published research on pharmacogenetics variants that affect paclitaxel outcomes. This finding suggests that prior pharmacogenomics research findings may not be reproduced in the most frequently-diagnosed malignancy, lung cancer.
Identifiants
pubmed: 30817750
doi: 10.1371/journal.pone.0212097
pii: PONE-D-18-00240
pmc: PMC6394902
doi:
Substances chimiques
Taxoids
0
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0212097Subventions
Organisme : NCI NIH HHS
ID : ZIA BC010627
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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