Evaluating the Efficacy and Safety of 4% 5-Fluorouracil Cream in Patients with Actinic Keratosis: An Expert Opinion

Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak(®); Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors’ expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile. SIGNIFICANCE Actinic keratoses are lesions that appear on photodamaged skin (e.g. face, neck and upper limbs) preceding or accompanying invasive skin cancer and are typically treated with creams containing 5-fluorouracil. This article reviews clinical trial data on how a new cream containing 4% 5-fluorouracil performed in adults with actinic keratosis. Treatment with 4% 5-fluorouracil cream was highly efficacious, safe, and prevented disease recurrence in approximately 27% of patients who achieved complete clearance of lesions in phase 3 studies. However, all trials were performed in patients with severe disease and numerous actinic keratosis lesions, making it more difficult for more patients to achieve complete clearance. Thus, other endpoints, such as percentage change in lesion count, ≥75% clearance of lesions or clinically significant changes in validated severity scales,may better reflect the efficacy of 4% 5-fluorouracil.