High-dose oral vitamin D was associated with rapid symptomatic and objective improvement in chemotherapy- and radiation-associated toxic effects of the skin, with no treatment-related adverse events.
Researchers conducted a retrospective multicenter case series of 33 patients treated by oncodermatologists at 3 academic medical centers between December 2021 and January 2024. Patients had toxic erythema of chemotherapy (TEC) or acute radiation dermatitis (ARD), received 1 or 2 oral doses of 100,000 IU of cholecalciferol or ergocalciferol, and had at least 10 days of follow-up. The mean age was 60.9 years; 19 patients (58%) were female, 28 (85%) had TEC, and 5 (15%) had ARD.
The primary outcomes were time to patient-reported symptom relief and clinician-assessed improvement in erythema. Researchers retrospectively graded erythema on a 5-point Likert scale using clinical photographs or examination descriptions when photographs were unavailable. Secondary outcomes included changes in serum calcium and the ability to continue anticancer therapy.
Within 10 days, 26 of 30 patients (87%) with evaluable symptom data reported subjective symptom relief, and 23 (77%) had clinician-assessed clinical improvement. Median time to improvement was 5 days overall and 3 days among inpatients. Mean erythema scores decreased from 4.36 at baseline to 3.17 by day 5 and 2.21 by day 10, a 1.92-point reduction.
Anticancer therapy continued without interruption in 24 of 33 patients (73%). Four patients (12%) discontinued therapy because of skin toxic effects, including 3 with Stevens-Johnson syndrome/toxic epidermal necrolysis–like eruptions and 1 with severe hand-foot syndrome. Laboratory monitoring showed no meaningful changes in serum calcium, and posttreatment vitamin D levels remained normal in all 13 patients tested. No adverse events were attributed to high-dose vitamin D.
Erythema improved most rapidly in neutrophilic eccrine hidradenitis and Stevens-Johnson syndrome/toxic epidermal necrolysis–like eruptions and more slowly in flexural and intertriginous eruptions. Inpatients reported symptom relief sooner than outpatients, at a mean of 3.4 vs 6.3 days. Earlier administration for severe inpatient presentations and more consistent inpatient assessments may have contributed to the difference.
Interpretation of the findings was complicated by concomitant treatment. Prior supportive dermatologic therapy was documented in 22 patients (67%), while 30 (91%) received supportive treatment concurrently with high-dose vitamin D, most commonly topical corticosteroids in 28 patients (85%). Twenty-eight patients (85%) received a second vitamin D dose within 7 days; 5 received only 1 dose because their skin toxic effects resolved before day 7.
The study was limited by its retrospective design, lack of a placebo or untreated control group, variable follow-up, potential selection bias, incomplete laboratory data, and use of a novel, nonvalidated erythema scale. With only 5 patients with ARD, conclusions specific to radiation-associated skin toxic effects were also limited. Researchers called for prospective controlled trials with standardized toxicity grading, protocolized laboratory monitoring, and longer follow-up to establish efficacy, durability, long-term safety, and optimal dosing. They also called for studies of prophylactic high-dose vitamin D to prevent treatment-related skin toxic effects.
The findings suggest high-dose oral vitamin D warrants further study as supportive care for chemotherapy- and radiation-associated skin toxic effects, but the uncontrolled design and frequent concomitant therapy preclude attributing the observed improvements to vitamin D alone. High-dose vitamin D “warrants further exploration to define its role in the evolving oncodermatology landscape,” wrote co–first study author Mihir K. Patil, BS, of Carle Illinois College of Medicine and the Department of Dermatology and Center for Cutaneous Oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, and colleagues.
Guggina reported personal fees from Synox Therapeutics. Nambudiri reported royalties, honoraria, and grants from multiple organizations. Full disclosures can be found in the study.
Source: JAMA Dermatology
