Evaluating Safety and Efficacy of Combination Therapy with Short-Contact Topical 5-Fluorouracil 5% and Calcipotriene for Actinic Keratoses

Background: Actinic Keratoses (AKs) are precancerous lesions to squamous cell carcinomas of the skin, affecting roughly 35% of adults over the age of 40. The lesions are directly linked to the cumulative exposure to UV radiation and arise from keratinocyte dysplasia. Standard treatment includes liquid nitrogen (LN2), topical 5-Fluorouracil creams (5-FU), or combination therapy. Vitamin D derivatives have demonstrated anti-proliferative properties in cancer treatment via stimulation of the vitamin D3 receptor and, therefore, may be efficacious in the treatment of AKs. However, these treatments are limited by side effects such as pruritus, erythema, dryness, and irritation. Objective: The purpose of this study is to evaluate the safety and efficacy of short-contact combination therapy of topical 5-FU 5% cream and vit D foam after LN2. Methods: This was a retrospective study on adults diagnosed with AKs in a private clinical dermatology office setting. Charts from 139 patients, 49% males and 51% females, with a mean age of 57.4, were examined. All patients were first treated with LN2 at baseline. Short-contact therapy of topical 5-FU and/or vit D foam consisted of a thin application nightly to the face for 5 nights and to other treatment areas for 7 nights, and then no application for 2 weeks. The cycles were repeated every 3 weeks. The patients were divided into six treatment groups: 1) 5-FU 5% after LN2, 2) vit D foam after LN2, 3) 5-FU 1% after LN2, 4) 5-FU 5% and vit D foam after LN2, 5) 5-FU 1% and vit D foam after LN2, and 6) LN2 alone. AKs of the of the face, scalp, chest, upper extremities, back, and lower extremities for each patient were documented at baseline and follow up visits at 20-50, and 51-100 days. An analysis of covariance (ANCOVA) model was used to compare post-treatment lesion counts between treatment groups at 95% confidence intervals. Results/Conclusions: Greater irritation was observed with the 5-FU 5% cream compared to other treatment groups. Short-contact combination therapy with 5-FU cream and Vit D foam after LN2 demonstrates increased efficacy over LN2 alone. Studies with an increased sample size for a longer duration should be performed to evaluate efficacy and safety.