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.
Chemotherapy-Induced Cutaneous Events Treated with High-Dose Vitamin D
Chemotherapeutic agents are known to induce cellular damage, resulting in a range of cutaneous AEs that can invoke discontinuation of otherwise effective chemotherapeutic interventions.27,28 Recent research has explored the potential of high-dose vitamin D3 as a therapeutic agent to mitigate cutaneous reactions.29,30
A randomized, double-blind, placebo-controlled trial investigated the use of a single high dose of oral 25(OH)D to treat topical nitrogen mustard (NM)–induced rash.29 To characterize baseline inflammatory responses from NM injury without intervention, clinical measures, serum studies, and tissue analyses from skin biopsies were performed on 28 healthy adults after exposure to topical NM—a chemotherapeutic agent classified as a DNA alkylator. Two weeks later, participants were exposed to topical NM a second time and were split into 2 groups: 14 patients received a single 200,000-IU dose of oral 25(OH)D while the other 14 participants were given a placebo. Using the inflammatory markers induced from baseline exposure to NM alone, posttreatment analysis revealed that the punch biopsies from
Although Ernst et al29 did not observe any clinically significant improvements with VD treatment, a case series of 6 patients with either glioblastoma multiforme, acute myeloid leukemia, or aplastic anemia did demonstrate clinical improvement of TEC after receiving high-dose vitamin D3.30 The mean time to onset of TEC was noted at 8.5 days following administration of the inciting chemotherapeutic agent, which included combinations of anthracycline, antimetabolite, kinase inhibitor, B-cell lymphoma 2 inhibitor, purine analogue, and alkylating agents. A combination of clinical and histologic findings was used to diagnose TEC. Baseline 25(OH)D levels were not established prior to treatment. The treatment regimen for 1 patient included 2 doses of 50,000 IU of VD spaced 1 week apart, totaling 100,000 IU, while the remaining 5 patients received a total of 200,000 IU, also split into 2 doses given 1 week apart. All patients received their first dose of VD within a week of the cutaneous eruption. Following the initial VD dose, there was a notable improvement in pain, pruritus, or swelling by the next day. Reduction in erythema also was observed within 1 to 4 days.30
No AEs associated with VD supplementation were reported, suggesting a potential beneficial role of high-dose VD in accelerating recovery from chemotherapy-induced rashes without evident safety concerns.
