Comparison of topical 5-fluorouracil formulations in actinic keratosis treatment

Actinic keratoses (AKs) are common and may progress to squamous cell carcinoma (SCC). While cryotherapy is the most commonly used treatment for AKs, it is only suitable for treating a few lesions at a time. Topical medications such as 5-fluorouracil (5-FU) allow for more generalized treatment of AKs in the setting of multiple lesions.

To evaluate and discuss clinical trials examining the efficacy of 5-FU cream formulations (0.5% and 5%), as 5% 5-FU has four times greater systemic absorption.

We conducted Pubmed and Embase searches (1965 to 13 April 2009) to find studies evaluating the efficacy of 5-FU cream monotherapy (0.5% and 5%) in treating multiple AKs of the face and scalp. We only included studies employing standard treatment regimens (as per the US FDA), with an endpoint of complete clearance.

Nine studies met our criteria. At 4 weeks post-treatment, complete clearance rates of 0.5% and 5% 5-FU ranged from 16.7% to 57.8% and 43% to 100%, respectively. As the various studies employed different measurements of tolerability, we were unable to pool this data. In the only split-face study comparing both formulations, both treatments produced equivalent rates (43%) of complete clearance, but 5% 5-FU had higher rates of adverse events.

Despite evidence suggesting the superior efficacy of 5% 5-FU over 0.5% 5-FU, high-powered clinical trials comparing both treatments are lacking. Furthermore, tolerability rates between formulations warrant further examination given the possible enhanced systemic absorption of 5% 5-FU over 0.5% 5-FU. Such studies will enable dermatologists to appropriately balance the risks and benefits of each respective treatment to provide optimal solutions to patients with multiple AKs.