Use of reflectance confocal microscopy to evaluate 5-fluorouracil 0.5% /salicylic acid 10% in the field-directed treatment of sub-clinical lesions of actinic keratosis: sub-analysis of a Phase III, randomised, double-blind, vehicle-controlled trial

Abstract

Background

Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or sub-clinical (invisible) lesions within areas of chronic sun damage. The importance of treating sub-clinical AK is gaining support. We present a sub-analysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5% /salicylic acid 10% treatment of sub-clinical AK lesions, based on reflectance confocal microscopy (RCM).

Objective

To determine the efficacy of 5-FU 0.5% /salicylic acid 10% as field-directed treatment for sub-clinical AK lesions using RCM.

Methods

For inclusion in this sub-analysis, patients had to have at least three sub-clinical AK lesions within a 25 cm² area of skin. Sub-clinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Sub-clinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5% /salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment.

Results

Twenty-seven patients were included: 17 (mean age = 72.2 years, standard deviation [SD] = 6.3) received 5-FU 0.5% /salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of sub-clinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06–0.57) for the 5-FU 0.5% /salicylic acid 10% group and 1.6 (95% CI 0.52–2.68) in the vehicle group (reductions of 90% [95% CI 72.1–107.1] vs. 47% [95% CI 24.8–69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5% /salicylic acid 10% showing complete clearance of three pre-selected sub-clinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183).

Conclusion

To the best of our knowledge, this is the first randomised, vehicle-controlled study investigating 5-FU 0.5% /salicylic acid 10% treatment for sub-clinical AK lesions. The present data suggest some treatment efficacy for sub-clinical AK lesions detected using RCM. However, this sub-analysis was not sufficiently powered and should be reproduced in a larger, subsequent cohort.

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