Comparison of topical 5-fluorouracil formulations in actinic keratosis treatment

Abstract

Despite evidence suggesting the superior efficacy of 5% 5-FU over 0.5% 5-FU, high-powered clinical trials comparing both treatments are lacking. Furthermore, tolerability rates between formulations warrant further examination given the possible enhanced systemic absorption of 5% 5-FU over 0.5% 5-FU. Such studies will enable dermatologists to appropriately balance the risks and benefits of each respective treatment to provide optimal solutions to patients with multiple AKs.

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

“…A similar percentage of participants in both groups reported scaling and itching of the treated skin during the 4-day treatment period (Table 2). No crusting or wounding was observed on the skin of the study participants, whereas such morbidities are common in response to 2 to 4 weeks of 5-FU cream treatment (Supplemental Figure 13) (21). No pain, scarring, oozing, vesiculation, pustulation, pigmentary changes, or participants (P <0.0001 for all anatomical sites; Supplemental Figure 4).…”

“…Therefore, we hypothesized that combining 0.005% calcipotriol ointment with 5% 5-FU cream would heighten the immune-activating potential of calcipotriol. 5-FU is the standard of care for field treatment of actinic keratosis (21). As a monotherapy, 5-FU is used twice daily for 2 to 4 weeks in order to be effective (21); however, a shorter duration of 5-FU treatment may still induce the immunostimulatory signals (22) needed to fully activate the adaptive immune cells responding to a lower dose of calcipotriol.…”

“…5-FU is the standard of care for field treatment of actinic keratosis (21). As a monotherapy, 5-FU is used twice daily for 2 to 4 weeks in order to be effective (21); however, a shorter duration of 5-FU treatment may still induce the immunostimulatory signals (22) needed to fully activate the adaptive immune cells responding to a lower dose of calcipotriol. Hence, in a randomized, double-blind clinical trial, we examined the efficacy and safety of treatment with Although the primary and secondary endpoints of the study were focused on the elimination of the actinic keratoses, participants with hypertrophic actinic keratoses in the calcipotriol plus 5-FU group experienced marked reductions in the size of their hypertrophic lesions after treatment (Supplemental Figure 7).…”

“…Actinic keratoses were clinically defined as pink, scaly papules on sun-damaged skin. A 4-day treatment duration was chosen, because 5-FU monotherapy has minimal impact on actinic keratosis clearance after 4 days (21). The drug combinations were prepared by mixing 0.005% calcipotriol ointment (Taro Pharmaceuticals) with 5% 5-FU cream (Taro Pharmaceuticals) or Vaseline with 5% 5-FU cream at a 1:1 weight ratio in accordance with United States Pharmacopeial Convention 795 (USP 795) guidelines for compounding topical medications and under the supervision of the investigational drug pharmacies of Washington University and Massachusetts General Hospital.…”

Management of actinic keratosis

“…Although it is quick and easy to perform, and does not require local anaesthesia, it does not allow histological examination of tissue, and it is only suitable for treating a few lesions at a time; thinner lesions have a higher response rate than thicker ones 14–16. It does not address adjacent field changes in the skin, where new lesions may develop over time 17.…”