Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221

作者：Ciao-Sin Chen, Gary Zirpoli, William Eric Barlow, George Thomas Budd, Bryan McKiver, Lajos Pusztai, Gabriel N. Hortobágyi, Kathy S. Albain, Mohamad Imad Damaj, Andrew K. Godwin, Alastair Mark Thompson, N. Lynn Henry, Christine B. Ambrosone, Kathleen A. Stringer, Daniel L. Hertz · 发表于：Journal of the National Comprehensive Cancer Network · 年份：2023 · DOI：10.6004/jnccn.2023.7062 · 被引用次数：30 · 研究领域：Cancer Treatment and Pharmacology、HER2/EGFR in Cancer Research、Pain Mechanisms and Treatments

BACKGROUND: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor. METHODS: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier: NCT00070564) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D-deficient diet. RESULTS: Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14-2.15; P=.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18-2.30; P=.00...