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

• Published in: Dermatology and therapy Vol. 7; no. 1; pp. 81 - 96
• Main Authors: Stockfleth, Eggert, von Kiedrowski, Ralph, Dominicus, Rolf, Ryan, John, Ellery, Adam, Falqués, Meritxell, Ivanoff, Nathalie, Azeredo, Rosario Rodriguez
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.03.2017; Springer Nature B.V
• Subjects: Dermatology; Internal Medicine; Medicine; Medicine & Public Health; Oral and Maxillofacial Surgery; Original Research; Plastic Surgery; Quality of Life Research; Hyperkeratotic lesion; 5-Fluorouracil/salicylic acid; Actinic keratosis; Topical treatment; Field-directed treatment; Field cancerization
• ISSN: 2193-8210; 2190-9172
• DOI: 10.1007/s13555-016-0161-2

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 cm 2 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.