Pre-treatment vitamin D insufficiency predicts severe paclitaxel-induced sensory neuropathy in breast cancer patients: a prospective cohort study

Abstract

Paclitaxel-induced peripheral neuropathy (CIPN) is a debilitating side effect affecting up to 70% of patients receiving paclitaxel chemotherapy, with severe symptoms occurring in approximately 30%. While non-modifiable risk factors such as age and genetics have been established, the role of modifiable factors, including vitamin D insufficiency, remains poorly characterized. This study aimed to evaluate the association between pre-treatment vitamin D levels and the incidence of severe CIPN in breast cancer patients receiving paclitaxel-based chemotherapy. A prospective cohort study was conducted on 300 breast cancer patients (stage I-III) receiving paclitaxel-based chemotherapy (80 mg/m²) for 12 weeks at Kafrelsheikh University Hospitals. Baseline serum 25(OH)D was quantified using the Elecsys Vitamin D Total II assay on the Cobas e411 platform, standardized to the VDSP reference method. Pre-treatment vitamin D levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with insufficiency defined as ≤ 20 ng/mL. CIPN was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-item scale (EORTC QLQ-CIPN20), with particular focus on grade 3-4 sensory neuropathy. Statistical analyses included receiver operating characteristic (ROC) curves and multivariate logistic regression to identify independent risk factors. The mean pre-treatment vitamin D level was 23.45 ± 8.3 ng/mL, with 39.3% (118/300) of patients classified as having vitamin D insufficiency. Patients with vitamin D insufficiency demonstrated significantly higher rates of grade 3-4 sensory CIPN compared to those with sufficient levels (32.2% vs. 5.5%, p < 0.001). Mean vitamin D levels were significantly lower in patients who developed severe CIPN (17.5 ± 4.9 ng/mL vs. 24.6 ± 8.4 ng/mL, p < 0.001). ROC analysis demonstrated vitamin D's predictive value for motor CIPN (AUC = 0.747, p = 0.038). Multivariate logistic regression analysis confirmed vitamin D insufficiency as an independent predictor of sensory CIPN (OR = 6.72, 95% CI: 3.09-14.61, p < 0.001), even after adjusting for age, body mass index, and treatment schedule. Vitamin D insufficiency is independently associated with an increased risk of severe paclitaxel-induced peripheral neuropathy in breast cancer patients. While causal inference cannot be drawn from this observational design, these findings provide a strong rationale for future randomized controlled trials to evaluate whether vitamin D supplementation could serve as a candidate preventive strategy to mitigate CIPN severity and optimize cancer therapy outcomes.