Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients.
chemotherapy-induced peripheral neuropathy
metastatic breast cancer
nab-paclitaxel
single nucleotide polymorphism
taxane-induced peripheral neuropathy
Journal
Acta medica Okayama
ISSN: 0386-300X
Titre abrégé: Acta Med Okayama
Pays: Japan
ID NLM: 0417611
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
entrez:
22
12
2022
pubmed:
23
12
2022
medline:
27
12
2022
Statut:
ppublish
Résumé
Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients' quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001-3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01).
Substances chimiques
130-nm albumin-bound paclitaxel
0
taxane
1605-68-1
Taxoids
0
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
661-671Déclaration de conflit d'intérêts
No potential conflict of interest relevant to this article was reported.
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