Chemotherapy-induced peripheral neuropathy (CIPN) remains a significant challenge in cancer treatment, particularly with agents like paclitaxel. A study published in the Journal of the National Comprehensive Cancer Center delves into the association between pretreatment vitamin D insufficiency and the incidence of CIPN in patients with early-stage breast cancer undergoing paclitaxel-based chemotherapy.
CIPN, affecting up to 70% of paclitaxel-treated patients, can persist for years, compromising patients' long-term quality of life. While duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, effectively addresses CIPN pain, preventive and treatment strategies for sensory or motor CIPN symptoms are lacking. Previous research hinted at vitamin D insufficiency as a potential risk factor, but validation through well-conducted studies was warranted.
The prospective-retrospective analysis utilized data from the SWOG S0221 clinical trial, encompassing 1,191 female participants receiving paclitaxel. Patients with pretreatment vitamin D insufficiency exhibited a higher incidence of grade ≥3 sensory CIPN. The association retained significance after adjusting for age and paclitaxel schedule but lost significance when further adjusted for self-reported race. Secondary analyses reaffirmed the link, using a combination of sensory and motor CIPN as the dependent variable.
Using a C57BL/6J mouse model, the study demonstrated that vitamin D deficiency induced mechanical hypersensitivity and worsened paclitaxel-induced hypersensitivity. The findings supported that vitamin D insufficiency might directly contribute to neurotoxicity, potentially explaining the higher incidence of CIPN in vitamin D–insufficient patients.
Implications and Future Directions: The results imply a critical role for vitamin D in CIPN risk, emphasizing the need for prospective trials on vitamin D supplementation for CIPN prevention. The study acknowledged its limitations, including the lack of detailed dosing information and the need for more diverse participant cohorts. Prospective trials exploring vitamin D supplementation as a preventive measure for CIPN are warranted, offering a promising avenue to enhance patients' quality of life and treatment outcomes during paclitaxel-based chemotherapy.
Sources: Journal of the National Comprehensive Cancer Center