Treatment of Actinic keratosis: topical ingenol mebutate versus 5%5-fluorouracil versus 5% imiquimod versus photodynamic therapy.

Rationale: Skin cancer is the most common cancer in Caucasians and therefore a major public health issue. Its incidence is increasing rapidly. Actinic keratosis (AK) is the most prevalent precancerous chronic skin condition. It can transform into squamous cell carcinoma (SCC). AK¡¯s generally arise in a skin area that has diffuse precancerous damage, a phenomenon called field cancerization. Because of its precancerous character, it is advised to treat AK and herewith prevent development into SCC. The most frequently used field-directed treatments in the Netherlands are photodynamic therapy (PDT), topical 5% f-fluorouracil (5% 5-FU) and topical 5% Imiquimod (5% IMI). Lately another topical product is approved by Dutch healthcare insurances: Ingenol mebutate (IM). Up to date, which treatment the patient will receive, does not rely on evidence-based-medicine, but generally on the preference of the physician. Current national and international guidelines state no clear recommendations for the best choice of therapy. The aim of this study is to investigate what is the most effective field-directed treatment for AK.
Objective: Determine which treatment is the most effective treatment in terms of lesion reduction, costs and patient satisfaction when comparing topical treatment with photodynamic therapy (PDT), 5% 5-fluorouracil (5-FU) cream, 5% Imiquimod (IMI) cream and 0.015%ingenol mebutate (IM) gel, in treatment of actinic keratosis (AK)
Study design: Prospective randomized controlled multi-centre study.
Study population: Patients, >18 years, Fitzpatrick skintype I-IV, with an area of minimal 25cm2 and maximal 100 cm2 AK, Olsen grade I-III, localized in the head,- and neck area, visiting Dermatology departments of the Maastricht University Medical Centre (MUMC), Catharina hospital Eindhoven, Atrium Medical Centre Heerlen or VieCuri Medical Centre Venlo.
Intervention: PDT versus 5% 5-FU versus 5% IMI versus 0.015% IM.
Main study parameters/endpoints: Primary outcome measure is adequate treatment success, defined as the proportion of participants at 12 months post treatment, with ¡Ý 75% reduction in the number of AK lesions counted at baseline in the treatment area. Secondary outcomes: partial response (proportion of participants with 50-75% reduction in number of AK lesions after 12 months compared to baseline), treatment failure (proportion of participants with <50% reduction in number of AK lesions after 12 months compared to baseline), partial lesion clearance (proportion of lesions with ¡Ý75% clearance), complete lesion clearance (proportion of lesions with 100% clearance in all treated patients), decrease in number AK from baseline per patient, costs, side effects, patient satisfaction, cosmetic outcome and treatment compliance, proportion of patients who develop SCC in treated areas.

Primary outcome is to define the treatment success of four topical treatment modalities for AK. We expect topical 5-flourouracil to be the most cost-effective treatment.

3 and 12 months follow-up time

Ingenol mebutate versus 5% 5-fluorouracil versus 5% imiquimod versus photodynamic therapy