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

Yuko Abe, Naruto Taira, Kosuke Kashiwabara, Junji Tsurutani, Masahiro Kitada, Masato Takahashi, Hiroaki Kato, Yuichiro Kikawa, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Tsutomu Takashima, Tomohiko Aihara, Hirofumi Mukai, Fumikata Hara, Tadahiko Shien, Hiroyoshi Doihara, Shinichi Toyooka

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish
Pages (from-to)661-671
Number of pages11
JournalActa medica Okayama
Volume76
Issue number6
DOIs
Publication statusPublished - Dec 1 2022

Keywords

  • chemotherapy-induced peripheral neuropathy
  • metastatic breast cancer
  • nab-paclitaxel
  • single nucleotide polymorphism
  • taxane-induced peripheral neuropathy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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