Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial.

INTRODUCTION: Due to the high prevalence of actinic keratosis (AK) and potential for lesions to become cancerous, clinical guidelines recommend that all are treated. The objective of this study was to evaluate the efficacy and safety of 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% as field-directed treatment of AK lesions. METHODS: This multicenter, double-blind, vehicle-controlled study (NCT02289768) randomized adults, with a 25 cm2 area of skin on their face, bald scalp, or forehead covering 4-10 clinically confirmed AK lesions (grade I/II), 2:1 to treatment or vehicle applied topically once daily for 12 weeks. The primary endpoint was the proportion of patients with complete clinical clearance (CCC) of lesions in the treatment field 8 weeks after the end of treatment. Secondary endpoints included partial clearance (PC; ≥75% reduction) of lesions. Safety outcomes were assessed. RESULTS: Of 166 patients randomized, 111 received 5-FU 0.5%/salicylic acid 10% and 55 received vehicle. At 8 weeks after the end of treatment, CCC was significantly higher with 5-FU 0.5%/salicylic acid 10% than with vehicle [49.5% vs. 18.2%, respectively; odds ratio (OR) 3.9 (95% CI) 1.7, 8.7; P = 0.0006]. Significantly more patients achieved PC of lesions with treatment than with vehicle [69.5% vs. 34.6%, respectively; OR 4.9 (95% CI 2.3, 10.5); P < 0.0001]. Treatment-emergent adverse events, predominantly related to application- and administration-site reactions, were more common with 5-FU 0.5%/salicylic acid 10% than with vehicle (99.1% vs. 83.6%). CONCLUSIONS: Compared with vehicle, field-directed treatment of AK lesions with 5-FU 0.5%/salicylic acid 10% was effective in terms of CCC. Safety outcomes were consistent with the known and predictable safety profile. TRIAL REGISTRATION: NCT02289768. FUNDING: Almirall S.A.

Low-Dose 0.5% 5-Fluorouracil/10% Salicylic Acid Topical Solution in the Treatment of Actinic Keratoses.

BACKGROUND: Actinic keratosis (AK) lesions have the potential to develop into invasive squamous cell carcinomas (SCCs), and approaches to treatment are evolving to try to reduce the burden of SCC. OBJECTIVE: To present the published clinical research surrounding the use of 0.5% 5-fluorouracil with 10% salicylic acid (low-dose 5-FU/SA) for the treatment of hyperkeratotic AKs. METHOD: A review of published clinical evidence for low-dose 5-FU/SA for the treatment of AKs. The articles were selected following a MEDLINE database search of the combined terms fluorouracil, salicylic acid and actinic keratosis which represent the peer review publications of clinical studies that primarily investigate the use of Actikerall in AK. RESULTS: Combining low-dose 5-FU with keratolytic SA is associated with high rates of histologic clearance, reduction in lesion number/area, and sustained clinical response in clinical study and the clinical practice setting. Low-dose 5-FU/SA has also been evaluated using imaging to detect the progression of subclinical AK lesions through a course of the field-directed treatment. CONCLUSION: Low-dose 5-FU/SA is an effective and well-tolerated treatment option licensed for the lesion-directed treatment of mild-to-moderate hyperkeratotic AK lesions.