Low vitamin D levels linked to chemotherapy-induced peripheral neuropathy
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Key takeaways:
- Vitamin D insufficiency before chemotherapy associated with higher risk for peripheral neuropathy.
- Vitamin D supplementation may lower risk for high-grade chemotherapy-induced peripheral neuropathy.
Individuals with insufficient levels of vitamin D prior to treatment with paclitaxel are at higher risk for developing chemotherapy-induced peripheral neuropathy, study results showed.
Researchers published a retrospective analysis of data from the phase 3 SWOG S0221 trial in Journal of the National Comprehensive Cancer Network, along with results of a preclinical investigation demonstrating neurotoxicity among vitamin D-deficient mice exposed to paclitaxel.
“These results suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” Daniel L. Hertz, PharmD, PhD, associate professor at University of Michigan College of Pharmacy, said in an NCCN-issued press release.
“There are barely any negative consequences that come from taking steps to increase vitamin D levels,” Hertz added. “Patients can easily take safe, inexpensive and widely available over-the-counter supplements.”
Background
Chemotherapy-induced peripheral neuropathy is a common toxicity related to the use of paclitaxel and can often lead to treatment plan alterations that negatively affect outcomes, according to Chen and colleagues.
“Several retrospective studies suggested that patients with lower pretreatment vitamin D concentrations have higher [chemotherapy-induced peripheral neuropathy] risk; however, this has yet to be validated in a well-conducted retrospective analysis of a prospective clinical trial, referred to as a prospective retrospective study,” they wrote. “Validation of vitamin D insufficiency as a [chemotherapy-induced peripheral neuropathy] risk factor is a critical first step toward developing interventional strategies to prevent [it], extend chemotherapy treatment, and improve clinical outcomes.”
Methodology
Chen and colleagues conducted a retrospective analysis to determine whether vitamin D insufficiency is a risk factor for developing chemotherapy-induced peripheral neuropathy resulting from the use of paclitaxel.
The investigators used data and pretreatment vitamin D blood samples from the prospective randomized phase 3 SWOG S0221 trial examining the safety and efficacy of several paclitaxel-containing chemotherapy regimens in women with early-stage breast cancer.
They evaluated the association between vitamin D insufficiency — defined as a concentration of 20 ng/mL or less — and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy using multiple logistic regression analysis adjusted for self-reported race, age, BMI and paclitaxel treatment schedule (random assignment to weekly or every 2-week dosing).
The researchers also evaluated the effect of vitamin D deficiency by assessing mechanical hypersensitivity in mice exposed to paclitaxel after being randomly assigned to a regular or vitamin D-deficient diet.
Key findings
The analysis included 1,191 women (mean age, 51.1 years; 84% white; 46% premenopausal), one-third of whom had insufficient vitamin D levels prior to chemotherapy. A total of 195 patients (16.4%) eventually developed grade 3 or higher chemotherapy-induced peripheral neuropathy.
Researchers reported significantly higher risk for developing chemotherapy-induced peripheral neuropathy among those who had vitamin D insufficiency prior to treatment compared with those who had acceptable vitamin D levels (20.7% vs 14.2%; OR = 1.57; 95% CI, 1.14–2.15).
Multivariate analysis showed significant associations between vitamin D insufficiency prior to treatment and older patients and those assigned to receive paclitaxel once every 2 weeks. A univariate association between self-reported Black race did not retain statistical significance during univariate analysis.
Results from the preclinical experiment showed a significant and progressive decrease in mechanical sensitivity among paclitaxel-treated mice that received a vitamin D-restricted diet.
The researchers acknowledged several study limitations, with the most notable being that the original randomized trial did not collect information on grade 2 chemotherapy-induced peripheral neuropathy cases or maintain detailed documentation on paclitaxel dosing information.
Clinical implications
“This prospective-retrospective analysis of the SWOG S0221 study has revealed a significant association between vitamin D insufficiency and an increased incidence of chemotherapy-induced peripheral neuropathy,” Mei Wei, MD, a medical oncologist at Huntsman Cancer Institute at the University of Utah — who was not involved in the research — said in the release. “This study finding uncovers a new potential strategy to combat [chemotherapy-induced peripheral neuropathy], thereby improving the quality of life for cancer patients undergoing treatment.”
Wei — a member of the NCCN Clinical Practice Guidelines in Oncology Panel for Breast Cancer — said she eagerly anticipates results of another ongoing study led by Daniel Rotroff, PhD, at Cleveland Clinic examining genetic and inflammatory biomarkers that may be associated with development of chemotherapy-induced peripheral neuropathy.
“This research holds the promise of shedding future light on the mechanisms underlying [chemotherapy-induced peripheral neuropathy] and the potential identification of biomarkers that could predict [its] incidence,” Wei said.
References:
Chen C-S, et al. J Natl Compr Canc Netw. 2023;doi:10.6004/jnccn.2023.7062.
New research in JNCCN suggests a simple and inexpensive option for reducing a major chemotherapy side-effect (press release). Available at: https://www.nccn.org/home/news/newsdetails?NewsId=4291. Published Nov. 7, 2023. Accessed Nov. 7, 2023.
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