AT SID 2017

PORTLAND (FRONTLINE MEDICAL NEWS) – A standard course of topical 5-fluorouracil (5-FU) does not noticeably improve visual signs of facial photoaging, such as forehead lines and crow’s feet, according to the results of a blinded, controlled study of 281 elderly white men.

Four validated photonumeric measures revealed no statistically significant differences between the intervention and vehicle control arms at 6, 12, or 18 months’ follow-up, Kaveri Korgavkar, MD, said at the annual meeting of the Society for Investigative Dermatology. “This might be a true lack of impact, or current scales may not be sensitive enough to capture aspects of aging that are improved by 5-fluorouracil,” commented Dr. Korgavkar, who presented the findings on behalf of the VAKCCT (the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial) work group.

The trial included veterans from 12 sites in the United States. Patients were randomly assigned to apply either vehicle control cream or a standard course of topical 5% 5-FU twice daily on the face and ears for 4 weeks. They were photographed at baseline and during follow-up visits every 6 months for up to 48 months, said Dr. Korgavkar of Brown University, Providence, R.I. To examine the effects of 5-fluorouracil on photoaging, two blinded dermatologists separately evaluated 3,042 baseline and follow-up photographs of participants by using the 5-point Allergan Forehead Lines Scale , the 5-point Melomental Lines Grading Scale , the 5-point Crow’s Feet Grading Scale , and the 9-point Griffith’s scale for wrinkling, hyperpigmentation, and yellowing.

The treatment and control groups resembled each other demographically and clinically at baseline. Participants averaged 71.5 years of age (standard deviation, 0.57 years), 97% were male, 99% were white, and all had clinically meaningful histories of sun damage with at least two keratinocyte carcinomas in the previous 2 years, including at least one lesion on the face or ears. Previously, the VAKCCT investigators reported positive results for 5-FU as a chemopreventive – for example, it was associated with about a 60% reduction in actinic keratoses, compared with placebo, and the effects persisted for up to 3 years.

However, none of the four photonumeric scales of photoaging uncovered significant differences between the treatment and control groups at 6, 12, or 18 months’ follow-up, Dr. Korgavkar reported. That finding belies the results of two other previous studies, but they were small and uncontrolled, she added. One study of 19 patients reported statistically significant improvements over time in wrinkling, hyperpigmentation, lentigines, and sallowness based on the Griffith’s scale, while a second prospective study of 32 patients reported significant improvements in visual signs of photoaging on the forearms, with a corresponding rise in levels of procollagen 1 and a decrease in dermal elastosis at 1 month.

Existing scales might more effectively capture some aspects of photoaging – such as wrinkles or crow’s feet – than others, Dr. Korgavkar said in an interview. Therefore, she and her associates are working to construct more sensitive and comprehensive visual scales of photoaging, she said.

The VAKCCT was sponsored by the VA Office of Research and Development. Dr. Korgavkar had no conflicts of interest.


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