Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study

Background: Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin-based oleogel prepared from a standardized triterpene dry extract from birch bark represents a new topical agent with anti-inflammatory and anti-tumor potential. Patients and Methods: In the prospective, randomized, monocentric phase 2a study 45 patients with <= 10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel. Treatment response was assessed clinically after three months. The clinical response was graded into complete clearing (100 %), therapy responders (>= 75 % clearing of the lesions) and non-responders (< 75 % clearing). Additionally, punch biopsies were obtained from some patients before and at the end of treatment. Results: Therapy with betulin-based oleogel was well tolerated. Three patients discontinued therapy because of personal reasons. After three months, the 100 % (and > 75 %) clearing rates of the lesions were as follows: 64 % (86 %) with betulin-based oleogel (n = 14), 79 % (93 %) with cryotherapy (n = 14), and 71 % (71 %) with the combined therapy (n = 14). Histological analysis of biopsies taken before and after treatment (n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms. Conclusions: Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However, the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.