SCOTTSDALE – A single course of topical 5-fluorouracil (5-FU) prevented 62% more actinic keratoses than placebo, and this chemopreventive effect persisted for up to 3 years, according to an analysis of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCCT) trial.
Other studies have shown that 5-FU effectively treats precancerous AKs, but have not examined whether 5-FU can prevent AKs, Dr. Joanna Walker said in an interview at the annual meeting of the Society for Investigative Dermatology.
Clinicians should consider preventive 5-FU in patients who are at high risk for basal cell and squamous cell carcinomas, especially if a skin check reveals multiple AKs, said Dr. Walker of the department of dermatology, Brown University, Providence, RI.
The VAKCCT was a randomized, double-blind, placebo-controlled study conducted at 12 Veterans Affairs dermatology clinics. The 319 patients in the analysis were nearly all elderly men with extensive sun damage, with a total of 2,386 AKs at baseline, for an average of five lesions per patient. Patients also had a history of at least two keratinocyte carcinomas in the past 5 years, including at least one lesion on the face or ears, and no recent history of 5-FU exposure.
The clinically and demographically similar study arms were randomized to either 5% topical 5-FU cream or a vehicle control cream, applied twice daily for 2-4 weeks. Both groups received cryotherapy for existing AKs, and were given free SPF 30 sunscreen. At each 6-month follow-up visit, the researchers counted existing AKs and new lesions.
At month 6, the treatment group had 62% fewer new AKs than the placebo group (average per patient, 1.78 and 4.73, respectively), a statistically significant difference. At months 12, 18, 24, 30, and 36, respectively, the treatment group had 50%, 40%, 41%, 25%, and 35% fewer new AKs than the placebo group, and these differences all were statistically significant. Furthermore, at month 6, only 56% of treated patients had at least one new AK, compared with 78% of the control group (incidence rate ratio, 0.72; 95% confidence interval, 0.54-0.95).
This chemopreventive effect remained significant for 24 months, the investigators reported. “Individuals with at least five AKs at the time of 5-FU treatment had an even more dramatic reduction in new AKs,” Dr. Walker noted. “There is now high-quality evidence supporting the use of topical 5-FU for AK chemoprevention. I think this is important information that we can take back to the clinic when we are trying to convince our patients to go through a course of 5-FU.”
The rate of new AKs in the placebo group fell during the first 2.5 years of the study and then stabilized. “For both groups, there was a dramatic increase in the use of sunscreen during the trial, and we hypothesized that the decrease in AKs in the control group was due to increased use of sun-protective measures,” Dr. Walker said.
The research was funded by the Cooperative Studies Program of the U.S. Department of Veterans Affairs. Dr. Walker had no disclosures.