Benefits of High-Dose Vitamin D in Managing Cutaneous Adverse Events Induced by Chemotherapy and Radiation Therapy
The use of chemotherapy and radiation for cancer treatment can result in cutaneous adverse events (AEs) such as toxic erythema of chemotherapy (TEC) and radiation-induced dermatitis. High-dose vitamin D supplementation has been suggested to potentially improve and shorten recovery for these AEs, primarily based on data from case reports and case series. In this article, we discuss the role of vitamin D in the most prevalent cancers (breast and colorectal cancer) and changes in vitamin D levels after chemotherapy or radiation treatments. We also summarize reports on high-dose vitamin D supplementation for treating chemotherapy-induced and radiation-induced skin toxicity. Larger studies and randomized controlled trials are essential to clarify the roles of vitamin D in malignancy and in cutaneous AEs associated with cancer treatment. The existing studies we reviewed lack standardized dosing regimens and exhibited heterogeneity across study populations, making it challenging to draw generalizable conclusions.
Practice Points
- High-dose vitamin D supplementation may be considered in the management of cutaneous injury from chemotherapy or ionizing radiation.
- Optimal dosing has not been established, so patients given high-dose vitamin D supplementation should have close clinical follow-up; however, adverse events from high-dose vitamin D supplementation have not been reported.
Vitamin D (VD) regulates keratinocyte proliferation and differentiation, modulates inflammatory pathways, and protects against cellular damage in the skin. 1 In the setting of tissue injury and acute skin inflammation, active vitamin D—1,25(OH) 2 D—suppresses signaling from pro-inflammatory chemokines and cytokines such as IFN- γ and IL-17. 2,3 This suppression reduces proliferation of helper T cells (T H 1, T H 17) and B cells, decreasing tissue damage from reactive oxygen species release while enhancing secretion of the anti-inflammatory cytokine IL-10 by antigen-presenting cells. 2-4
Suboptimal VD levels have been associated with numerous health consequences including malignancy, prompting interest in VD supplementation for improving cancer-related outcomes.5 Beyond disease prognosis, high-dose VD supplementation has been suggested as a potential therapy for adverse events (AEs) related to cancer treatments. In one study, mice that received oral vitamin D3 supplementation of 11,500 IU/kg daily had fewer doxorubicin-induced cardiotoxic effects on ejection fraction (P<.0001) and stroke volume (P<.01) than mice that received VD supplementation of 1500 IU/kg daily.6
In this review, we examine the impact of chemoradiation on 25(OH)D levels—which more accurately reflects VD stores than 1,25(OH)2D levels—and the impact of suboptimal VD on cutaneous toxicities related to chemoradiation. To define the suboptimal VD threshold, we used the Endocrine Society’s clinical practice guidelines, which characterize suboptimal 25(OH)D levels as insufficiency (21–29 ng/mL [52.5–72.5 nmol/L]) or deficiency (<20 ng/mL [50 nmol/L])7; deficiency can be further categorized as severe deficiency (<12 ng/mL [30 nmol/L]).8 This review also evaluates the evidence for vitamin D3 supplementation to alleviate the cutaneous AEs of chemotherapy and radiation treatments.
