S. Mickan

Effectiveness of 5-fluorouracil treatment for actinic keratosis - A systematic review of randomized controlled trials

Actinic keratosis (AK) lesions present as dry, rough, yellow– brown, scaly plaques which may become thickened and horny. Most AKs are caused by chronic exposure to ultraviolet (UV) radiation and are therefore most common in middle-aged and elderly fair-skinned individuals. Regions with a higher UV exposure show a higher prevalence, and the incidence rate increases with age. 1 Around 15–25% of lesions resolve spontaneously over a 12-month period, and the risk of a single lesion progressing to an invasive squamous cell carcinoma (SCC) is in the range 0.25–20% per year. 2,3 Opinion differs about the classification of AKs – some argue that they should be classified as in situ SCC because they are histopathologically indistinguishable from SCCs, 3 whereas others argue that the classification of in situ SCC, although histopathologically correct, is liable to misinterpretation by consumers, leading to unnecessary and excessive concerns generated by a diagnosis of cancer and additional costs to already overburdened healthcare systems. 4 Nevertheless, the inability to predict which AK lesions will transform into invasive SCCs means that the treatment of all AKs is indicated. Topical 5-fluorouracil (5-FU) is a well-established treatment for AK. 5-FU is an antineoplastic antimetabolite, which interferes with the synthesis of DNA and RNA, provoking unbalanced cell growth and death. 5-FU enables field therapy for patients with multiple AKs, and may also promote the healing of subclinical lesions. 5 Treatment is lengthy (about 4 weeks) and application site reactions, ranging from redness, soreness and weeping to shallow ulceration and crusting, are a consequence of treatment. Despite the widespread use of 5-FU to treat AK, the evidence supporting its use has not been reviewed systematically or appraised critically, unlike that for imiquimod. 6–8 We therefore reviewed systematically the published literature to address this gap, and to identify areas in which further research is needed.