ORIGINAL ARTICLE Open label randomized study comparing 3 months vs. 6 months treatment of actinic keratoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of the German Dermatologic Cooperative Oncology Group A. Pflugfelder, †, * A.-K. Welter, † U. Leiter, † B. Weide, † L. Held, † T.K. Eigentler, † T. Dirschka, ‡ E. Stockfleth, – D. Nashan, § C. Garbe † † Centre for Dermatooncology, Department of Dermatology, University Hospital Tuebingen, Berlin, Germany ‡ Dermatological Practice Centre, Wuppertal, Germany § Department of Dermatology, University Medical Centre Freiburg, Berlin, Germany – Skin Cancer Centre Charite´ , Department of Dermatology, Charite´ Universita¨ tsmedizin Berlin, Berlin, Germany *Correspondence: A. Pflugfelder. Email: annette.pflugfelder@med.uni-tuebingen.de Abstract Background Actinic keratoses (AK) are carcinomata in situ with the potential to develop into invasive carcinoma. Several studies have demonstrated that 3% diclofenac in 2.5% hyaluronic acid gel (HA) is effective and well tolerated in the treatment of AK. To date there are no large randomized multicentre trials with treatment durations longer than 90 days and histopathological control of treatment outcome. Objective The aim of this study was to investigate whether a prolonged treatment with diclofenac in HA of 6 vs. 3 months adds to the efficacy in treatment for AK and if this will influence tolerability and quality of life (QoL). Methods This was a multicentre, randomized open-label study in which 418 patients with mild to moderate AKs were randomized into two treatment groups. Group A received diclofenac in HA for 3 months and group B for 6 months. Treatment efficacy was assessed by size measurement and a final biopsy of a defined marker AK. Quality of life was measured using the Dermatology Life Quality Index questionnaire. Results Clinical complete clearance was observed in 40% in group A and in 45% in group B (P = 0.38). Histopathological clearance was confirmed in 30% in group A and in 40% in group B (P = 0.16). Treatment was well tolerated and QoL was significantly improved after treatment in both treatment groups. Conclusion Treatment with diclofenac in HA is effective and well tolerated during a treatment period of 3 months as well as 6 months. Prolongation of the treatment duration did not significantly affect treatment outcome. Received: 13 September 2010; Accepted: 17 January 2011 Conflict of interest AP received honoria as speaker from Almirall and Shire, TD received honoria as speaker and investigator from Almirall, TKE received grants as speaker from Shire, CG received grants as investigator from Almirall. Funding sources Shire GmbH, Germany and Almirall, S.A., Spain. Introduction Actinic keratoses (AK) have a high incidence with up to 60% in individuals over 40 years in the southern hemisphere and with an increasing prevalence throughout the world in Cauca- sian persons. 1,2 They occur frequently in chronically sun exposed skin especially on face, scalp and arms. Important risk factors for AK are the combination of fair skin phenotype, cumulative sun exposure which leads to UV radiation-induced DNA damage and immunosuppression. AKs are clinically char- acterized by erythematous, keratotic macules, papules or pla- ques. Most patients present multiple lesions. Histopathologically an intraepidermal proliferation of atypical keratinocytes can be observed. These atypical keratinocytes can extend throughout the epidermis into the dermis and beyond and result in invasive squamous cell carcinoma (SCC). While AK was historically only seen as a ‘cosmetic problem’, AK is now considered as the beginning of a biological continuum that leads to invasive SCC. 1,3,4 ª 2011 The Authors JEADV 2012, 26, 48–53 Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology DOI: 10.1111/j.1468-3083.2011.04005.x JEADV