5-fluorouracil decreases rates of persistent and reappearing actinic keratoses: The VAKCC Trial

Moniyka Sachar1, Julia A Siegel1, Joanna L Walker1, Susan M Swetter2, George Stricklin3, Martin A Weinstock1, for the VAKCC Trial Group

1 VA Med Ctr, Brown Univ, Providence, RI

2 VA Healthcare Syst, Palo Alto, CA

3 VA Healthcare Syst, Nashville, TN

Keratinocyte carcinoma (KC) is the most common cancer in the United States, with over 5 million cases treated annually. KC treatment is associated with the potential for substantial morbidity as well as significant costs, estimated at $4.8 billion per year from 2007 to 2011. Actinic keratoses (AKs) are known precursors to squamous cell carcinoma (SCC) and therefore may be a target for KC prevention. Topical 5-fluoruracil (5-FU) has been shown to reduce AK count, but its role as AK prophylaxis (vs. treatment) is unclear. In this double-blind, placebo-controlled trial, veterans with two or more prior KCs were randomized to apply topical 5-FU or vehicle control cream to the face and ears twice daily for up to 4 weeks. Complete skin exams were performed by study dermatologists at enrollment and every 6 months, and clinically diagnosed AKs were marked, photographed, and later used to track AKs over time. This allowed distinction between new AKs and persistent AKs. Among participants in the placebo group who had had no AK treatments with cryotherapy on the face and ears from baseline to 6 months (n=161), only 15% (174/1160) of AKs persisted from baseline to 6 months, demonstrating a high rate of spontaneous regression. In the subset of the treatment group who had also not received cryotherapy on the face and ears during this time (n=152), only 5% (59/1177) of AKs persisted from baseline to 6 months—one third of the placebo group. At 6 months, the mean number of persistent AKs per subject was 1.09 in the placebo group and 0.39 in the treatment group (p<0.001). These findings suggest that 5-FU is effective in treating clinically apparent AKs and preventing them from persisting. Additionally, the high rate of spontaneous AK regression suggests that treating every AK with cryotherapy, as is commonly done in clinical practice, may often be unnecessary.