Daily application of topical fluorouracil for 4 weeks reduced the risk of developing squamous cell cancer (SCC) requiring surgery by 75% in a population of high-risk older adults.

The findings were published online Jan. 3 in JAMA Dermatology.

Although topical fluorouracil can help reduce actinic keratoses and cure some superficial basal cell and squamous cell carcinomas, it has not been studied as a strategy to prevent the development of lesions that might require surgery, wrote Martin A. Weinstock, MD, PhD, of Providence (R.I.) Veterans Affairs Medical Center, and his colleagues (JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631 ).

In the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial , researchers recruited patients at 12 Veterans Affairs medical centers who had a history of at least two keratinocyte carcinomas during the past 5 years. Participants were randomized to apply a 5% topical fluorouracil cream or a control cream to the face and ears twice daily for 4 weeks. The median age of the patients was 70 years and 98% were male.

Overall, 299 of the 932 participants developed a basal cell carcinoma and 108 developed an SCC over 4 years of follow-up (the median follow-up was 2.8 years). During the 4-year follow-up, no effect was seen on SCC or BCC.

But during the first year, significantly fewer participants in the fluorouracil group than in the control group developed an SCC (5 vs. 20), representing a 75% reduction in the risk of SCCs needing surgery (P = .002).

The number of participants who developed a BCC during the study period was not significantly different between the treatment and control groups (45 vs. 50). During the first year, the BCC risk was reduced by 11%, but it was not statistically significant.

Most patients in the treated group experienced erythema in the first 2 weeks, and more than half described adverse effects of treatment as severe (21%) or moderate (40%). But almost 90% said they would be willing to be treated again if the treatment was shown to reduce the risk of developing skin cancers, the authors wrote.

The study was limited by several factors including the potential unblinding of participants because of side effects and by the homogenous study population, the researchers noted. However, the results suggest the potential value of proactive topical treatment to reduce the need for surgery, they said. “It is reasonable at this point to consider the use of a standard and perhaps annual course of topical fluorouracil, 5%, to the face and ears for the reduction of SCC risk in high-risk populations, and potentially for a reduction in need for Mohs surgery; more detailed study could define precisely the groups that would most benefit,” they wrote.

Lead author Dr. Weinstock is employed by the dermatology practice affiliated with Brown University and is director of the dermatoepidemiology division at Brown. He disclosed serving as a consultant to AbbVie, Castle, and Celgene. Another author disclosed having received grant support from Pfizer for an independent research grant. The remaining 23 authors had no disclosures. The study was partly funded by the U.S. Department of Veterans Affairs.

SOURCE: Weinstock, M et al. JAMA Dermatol. 2017 Jan 3. doi: 10.1001/jamadermatol.2017.3631 .