Effect of Topical Fluorouracil Cream on Photodamage: Secondary Analysis of a Randomized Clinical Trial.

Importance: Photoaging, which is premature skin aging caused by long-term UV exposure, is of aesthetic concern to many patients. Objective: To investigate the effect of topical fluorouracil, 5%, cream on photoaging using validated photonumeric scales. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized clinical trial of 932 US veterans with a recent history of 2 or more keratinocyte carcinomas performed from September 30, 2011, through June 30, 2014, to assess the chemopreventive effects of a standard course of topical fluorouracil. Photographs were taken at baseline and at numerous time points for up to 4 years. In our secondary analysis, 2 independent dermatologists graded these photographs using 4 validated photonumeric scales. A total of 3042 photographs from 281 participants randomized to apply topical fluorouracil or placebo were evaluated at baseline, 6 months, 12 months, and 18 months using 4 photonumeric scales (Griffiths scale, Allergan forehead lines scale, melomental folds scale, and crow's feet scale). Data analysis was performed from November 1, 2016, to January 1, 2017. Interventions: Participants were randomized to apply topical fluorouracil, 5%, cream or a vehicle control cream to the face and ears twice daily for 2 to 4 weeks for a total of 28 to 56 doses. Main Outcomes and Measures: Effect of a standard course of fluorouracil on the extent of photodamage as measured using 4 photonumeric scales.
Results: The study population was predominantly male (274 [97.5%]) and white (281 [100%]), with a mean (SD) age of 71.5 (0.57) years. No statistically significant changes were found in photodamage between baseline and 6 months (Griffiths scale: χ2 = 0.01, P = .93; Allergan forehead lines scale: χ2 = 0.18, P = .67; melomental fold scale: χ2 = 0.03, P = .87; crow's feet scale: χ2 = 2.41, P = .12), 12 months (Griffiths scale: χ2 = 1.39, P = .24; Allergan forehead lines scale: χ2 = 0.64, P = .43; melomental fold scale: χ2 = 0.12, P = .73; crow's feet scale: χ2 = 1.07, P = .30), and 18 months (Griffiths scale: χ2 = 3.11, P = .08; Allergan forehead lines scale: χ2 = 0.89, P = .34; melomental fold scale: χ2 = 1.64, P = .20; crow's feet scale: χ2 = 0.46, P = .50). Conclusions and Relevance: This study did not demonstrate improvement in photoaging with a standard course of topical fluorouracil, 5%, cream, a finding that may be attributable to a true lack of effect in photodamage or limitations of the photonumeric scales in capturing the effect. The development of photonumeric scales that include manifestations of photoaging other than rhytids, such as lentigines, hyperpigmentation, and telangiectasias, should be considered. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

RCT Entities:   Population Interventions Outcomes