Randomized, Vehicle-controlled Trials of Topical 5-fluorouracil Therapy for Actinic Keratosis Treatment

An Overview

Maral Rahvar; Sonia A Lamel; Howard I Maibach


Immunotherapy. 2012;4(9):939-945. 

In This Article


Our database search identified 103 potential studies for efficacy evaluation. Seventy seven articles were excluded after reviewing available titles and abstracts. The remaining 26 articles were screened for study design inclusion elements and the presence of a vehicle control group. Four trials met criteria and their data were abstracted for analysis (Table 1).[22–25]

In the four trials, a total of 399 participants were in active treatment groups and 269 were in vehicle control groups. All studies required patients to be aged 18 years or older with at least five AKs on the face or frontal scalp for eligibility. Two studies included females only as long as they were not pregnant or lactating and were either postmenopausal or using appropriate contraceptives.[22,23] The presence of confounding skin conditions such as SCC or basal cell carcinoma, a history of drug allergy, or recent treatment of AK were common exclusion criteria.

Demographics and baseline characteristics were similar across all trials and in both the active treatment and vehicle groups (Table 2). The mean age of the active treatment groups was 62.7 years. The majority of patients were male (85.4%) and 89% had a Fitzpatrick skin type of either I or II. In the vehicle treatment groups, the mean age was 62.9 years, 85.8% of the patients were male and 93.6% had a Fitzpatrick skin type of I or II.[22–24]

All four trials evaluated 0.5% topical 5-FU and assessed changes in AKs after 4 weeks of therapy. Two trials assessed a once-daily regimen for 1, 2 and 4 weeks,[24,25] while the other two trials assessed a once-daily regimen for 1 week.[22,23]

The percentage of patients achieving complete clearance of their AKs in the 5-FU group was 19, 28.2 and 52.6% in the 1-, 2- and 4-week treatment groups, respectively. The percentage of patients reaching complete clearance in the vehicle-treated group was 0.85%.

The mean baseline and post-treatment AK counts are listed in Table 3. For the four trials, the mean baseline AK count was 14.2 in the 5-FU group and 14.45 in the vehicle-treated group. After 1 week of treatment, the mean lesion count was 4.2 in the active treatment group, resulting in a 9.7-lesion decrease from baseline (13.9). The mean post-treatment lesion count in the vehicle groups was 11.4, showing a mean lesion count reduction of 3.05.[22–24] The percentage reductions in AK counts (derived from least squares mean reduction) were 68.2, 84.2, 90.2 and 28.3% in the 1-, 2- and 4-week 5-FU and vehicle groups, respectively. Additionally, the range of percentage reduction in lesion counts noted in the vehicle groups ranged from 21.6 to 34.4%.