Vitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221.

Abstract

12023 Background: Peripheral neuropathy (PN) is a treatment-limiting toxicity of paclitaxel. Black patients have higher rates of PN and vitamin D insufficiency, and our prior work suggests vitamin D insufficiency increases risk of paclitaxel-induced PN. The objective of this study was to validate that patients with vitamin D insufficiency have higher risk of paclitaxel-induced PN and investigate whether this explains racial disparities in PN risk. Methods: This retrospective validation study was conducted in the phase III SWOG 0221 (NCT00070564) trial comparing paclitaxel-containing chemotherapy regimens for early-stage breast cancer. Pre-treatment 25-hydroxy-vitamin D was quantified in cryopreserved serum. Males and patients who received less than a third of the paclitaxel treatment were excluded. The association between vitamin D insufficiency (≤20 ng/mL) and grade 3+ sensory PN was tested via logistic regression and then adjusted for self-reported race, age, paclitaxel schedule (QW vs Q2W), and body mass index. Results: Of the 1,116 female patients in the analysis, 169 (15.1%) experienced PN and 376 (33.7%) had vitamin D insufficiency. Vitamin D insufficiency was associated with higher PN risk (19.4% vs 13.0%, OR = 1.62, p = 0.005, Data Table). The association was borderline significant (OR = 1.44, p = 0.056) after adjustment for black race (OR = 2.41, p = 0.001), paclitaxel schedule (OR = 2.22, p < 0.001), and age (OR = 1.03, p = 0.005). Compared with white patients (n = 943), black patients (n = 99) had more prevalent vitamin D insufficiency (77.8% vs 28.6%, OR = 8.72, p < 0.001) and increased PN risk (29.3% vs 13.5%, OR = 2.66, p < 0.001); adjusting for vitamin D insufficiency decreased but did not eliminate the higher PN risk in black patients (OR = 2.23, p = 0.002). Conclusions: Vitamin D insufficiency increases risk of paclitaxel-induced PN and partially explains the higher risk of PN in black patients. Prospective trials are needed to test whether vitamin D supplementation lessens PN and reduces disparities in treatment outcomes. [Table: see text]