Combination Therapy with Short-Contact Topical Calcipotriene and 5-FU For Actinic Keratosis

Background: Actinic keratoses (AKs) are precursor lesions to squamous cell carcinoma that arise from dysplasia of keratinocytes, which is enhanced by long-term ultraviolet radiation exposure. Treatment of actinic keratoses has traditionally involved cryotherapy, or various topical therapies such as topical 5-fluorouracil (5-FU) monotherapy, or combination therapy with cryotherapy. Because of irritation with use of topical 5-FU, short-contact therapy with 5-FU in combination with cryotherapy has been reported. Vitamin D derivatives have also been reported as systemic anti-cancer agents, though clinical data for usage is limited mainly due to hypercalcemia as an adverse effect and dose-limiting factor. Recent research has suggested that topical Vitamin D derivatives such as calcipotriene may be safe and efficacious agents for the treatment of AKs. Objective: The aim of this study was to evaluate efficacy and safety of short-contact topical treatment with calcipotriene and 5-FU with cryotherapy in the treatment of AKs. Combination short-contact calcipotriene and 5-FU with cryotherapy will be compared to short-contact 5-FU with cryotherapy and cryotherapy alone to determine differences in efficacy and safety between the treatment modalities. Methods: Subjects were identified as eligible for inclusion in this study based on a clinical diagnosis of actinic keratosis and treatment with cryotherapy, 5-FU, and/or topical calcipotriene between 2016 to 2018. The patients were divided into three treatment groups: 1) short-contact combination treatment with calcipotriene and 5-FU with cryotherapy, 2) short-contact 5-FU and cryotherapy, and 3) cryotherapy alone. Patients were assessed for baseline lesions in the face, scalp, upper extremities, chest, back, and lower extremities, and again at 1 month follow-up, 3 months follow-up, and 6 months follow-up. An analysis of covariance (ANCOVA) model with terms for treatment and baseline lesion count as covariate was used to compare post-treatment lesion count between treatment groups estimated at 95% confidence intervals (95% CI). Results: Data was collected on 50 patients in each subset. After adjusting for imbalances in baseline count, a statistically significant reduction in number of AK lesions occured after 6 months of treatment with short-contact combination treatment with calcipotriene and 5-FU with cryotherapy in comparison to short-contact 5-FU with cryotherapy and to cryotherapy. The mean total lesion count at month 6 in the short-contact combination treatment with calcipotriene and 5-FU with cryotherapy was significantly lower than in the other 2 subsets. Conclusions: Addition of topical calcipotriene to short-contact combination treatment of topical 5-FU with cryotherapy may result in improved long-term outcomes for patients with actinic keratoses. Larger series must be done to confirm increased efficacy and safety.