先前的研究表明，维生素 D 不足的患者因紫杉醇而发生化疗引起的周围神经病变 (CIPN) 的风险可能更高。本研究的目的是验证维生素 D 不足作为 CIPN 危险因素。我们使用了前瞻性 III 期 SWOG S0221（ClinicalTrials.gov 标识符：NCT00070564）试验的数据和样本，该试验比较了早期乳腺癌的含紫杉醇化疗方案癌症。我们使用液相色谱-串联质谱靶向测定法对库存血清样品中的预处理 25-羟基维生素 D 进行了定量。我们通过多元 Logistic 回归测试了维生素 D 不足 (≤20 ng/mL) 与 ≥3 级感觉 CIPN 之间的关联，然后根据自我报告的种族、年龄、体重指数和紫杉醇时间表进行调整（随机化为每周或每2周给药）。我们还测试了维生素 D 缺乏对随机接受常规饮食或缺乏维生素 D 饮食的小鼠机械过敏的直接影响。在分析中的 1,191 名女性患者中，397 名 (33.3%) 患有治疗前维生素 D 不足，195 名 (16.4%) 患有治疗前维生素 D 不足。 %) 达到 ≥3 级 CIPN。维生素 D 不足的患者发生 3 级以上 CIPN 的发生率高于维生素 D 充足的患者（20.7% vs 14.2%；比值比 [OR]，1.57；95% CI，1.14-2.15；P=.005）。调整年龄和紫杉醇方案后，该关联仍然显着（调整后 OR，1.65；95% CI，1.18-2.30；P=0.003），但不存在种族（调整后 OR，1.39；95% CI，0.98-1.97；P=.003）。 066）。在小鼠实验中，缺乏维生素 D 的饮食会导致机械过敏，并使小鼠对紫杉醇敏感（均 P<.05）。治疗前维生素 D 不足是第一个经过验证的紫杉醇 CIPN 潜在可修改预测生物标志物。需要前瞻性试验来确定补充维生素 D 是否可以预防 CIPN 并改善乳腺癌和其他癌症类型患者的治疗结果。

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.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.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=.003) but not race (adjusted OR, 1.39; 95% CI, 0.98-1.97; P=.066). In the mouse experiments, the vitamin D-deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P<.05).Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.