Intensity of Local Skin Reactions During 5-Fluorouracil Treatment Related to the Number of Actinic Keratosis Lesions: A Post Hoc, Exploratory Analysis

Abstract

Introduction: Actinic keratoses (AK) are epithelial lesions caused by chronic skin exposure to ultraviolet light that can progress into squamous cell carcinoma. Although several treatments are effective, they are associated with severe skin reactions, which might be related to the extent of the disease. This study aimed to examine the relationship between the severity of local skin reactions during treatment with 5-fluorouracil 4% cream and the number of AK lesions at baseline. Methods: This post hoc analysis pooled data from two multicentre randomised phase III studies (HD-FUP3B-048, HD-FUP3B-049) in patients with AK treated with topical 5-fluorouracil 4% once daily (OD) or 5% twice daily (BID) for 4 weeks. First, we compared the severity, assessed using a numerical rating scale, of the local skin reactions between 5-fluorouracil 4% and 5%. Then, we investigated the relationship between the number of lesions at baseline and severe skin reactions with 5-fluorouracil 4% OD. Results: Safety data were included from 397 patients who had received 5-fluorouracil 4% (348 in study HD-FUP3B-048, 49 in study HD-FUP3B-049) OD and 342 (HD-FUP3B-048) who had received 5-fluorouracil 5% BID. For most skin reactions, severe ones were more common in patients treated with 5-fluorouracil 5% cream BID than in those treated with 5-fluorouracil 4% cream OD (P < 0.05). With 5-fluorouracil 4% OD, the incidence of severe erythema was significantly higher in patients with at least 10 lesions (46%) than in patients with 5–10 lesions (28%; P < 0.001). Similar results were observed for the other local skin reactions. Conclusion: Treatment with 5-fluorouracil 4% cream OD was associated with less severe local skin reactions than 5-fluorouracil 5% BID. The number of AK lesions at baseline seems to have predictive value regarding the severity of local skin reactions that appear during treatment.