November 10, 2008 (Orlando, Florida) — Fluorouracil cream 0.5%, applied for 4 weeks with a microparticle delivery system, significantly reduces actinic keratosis (AK) lesions on the posterior scalp, ears, neck, lips, arms, and hands, according to results from a large multicenter trial presented here at the American Society for Dermatologic Surgery (ASDS) 2008 Annual Meeting.
This study was presented in a poster session by lead investigator Dow Stough, MD, from Burke Pharmaceutical Research, in Hot Springs, Arkansas, and clinical assistant professor of dermatology at the University of Arkansas for Medical Sciences, in Little Rock.
Because this lower concentration of fluorouracil has been shown in 2 previous phase 3 studies to be safe and effective in treating AK of the face and/or anterior scalp, this trial was designed to evaluate its tolerability and efficacy on a daily basis in subjects with multiple AK lesions on different body sites. Dr. Stough's presentation reported data from the first of 2 treatment cycles. (Data from the second cycle will be reported at a later time.)
"Dermatologists have a long history of using fluorouracil for precancers, and that's nothing new," Dr. Stough told Medscape Dermatology after his presentation. "What is new is this product, which is a much lower formulation than other active drugs. We wanted to [know if it would] lower the efficacy at this lower amount. Also, no study had been done before that evaluated areas other than the face."
A total of 277 patients were enrolled in 25 centers across the United States, with a mean age of 67.4 years; 81.2% of the population were men. In addition, each subject had at least 5 visible AK lesions on the posterior scalp, ears, neck, lips, arms, and/or hands, with an additional 5 lesions on the face/anterior scalp. These lesions were counted and recorded by the investigative team prior to initial treatment.
During this observation cycle, all patients were given fluorouracil cream 0.5% to self-apply once daily to the designated lesion area for up to 4 weeks, as tolerated. They returned to their study center 4 weeks later (week 8) so that changes in lesion counts and lesion clearance could be assessed.
Results at week 8 showed statistically significant (P < .0001) decreases from baseline in the number of AK lesions on the ears (–80%), neck (–79%), lips (–77%), posterior scalp (–77%), arms (–63%), and hands (–56%).
Total AK lesion clearance was achieved for more than 62% of patients on the lips (79.1%), neck (64.7%), and ears (62.3%). In addition, 47.9% of patients were clear of lesions on the posterior scalp, 37.2% were clear on the arms, and 30.5% were clear on the hands. A total of 14% experienced complete clearance of AK lesions on all designated treatment areas.
Treatment-emergent adverse events were low. The most common were related to lesion-site reactions and included symptoms such as dryness, erythema, burning, erosion, edema, and pain. Most were reported as mild or moderate in intensity.
"The drug performed very well, with no indication of toxicity," reported Dr. Stough. "It was a big study and we're confident that study results will be the same in a clinical practice setting." He went on to praise the product's delivery system: "The microsponge is unique and concentrates the drug into the skin, almost as a reservoir into the skin. That delivery method is important and contributed to the favorable results we found."
Robert Weiss, MD, the newly elected president of the ASDS, told Medscape Dermatology that "this is a nice study with the lower-concentration microsponge technology of 5-fluorouracil. Some of the old formulations had 5 to 10 times that amount. Also, most of the other studies have been done purely on the face. But this one included the neck, the arms, the hands — which is nice, as was the large number of patients." Dr. Weiss, from the Maryland Laser Skin and Vein Institute, in Hunt Valley, was not involved in the trial.
He continued: "They had a high clearance rate, at greater than 62%. With this type of thing, you will never get 100% with anything. So that is a very good, acceptable percentage. Also, it was conducted at 25 centers with a 4-week course of applying it once daily, which is very reasonable and a very good protocol. I think this demonstrates that you really don't cut back on efficacy, you increase the tolerability, and the side effects were minimal.... It's highly effective in this formulation."
When asked if there is anything he would like to see in future studies with this product, Dr. Weiss replied: "You could try another treatment cycle to see if you could get an even higher percentage, particularly on the back of the hands. Or maybe you could do something to increase the percentage that reaches the skin, maybe twice daily for the hands to try to make it more effective. But overall, based on this study, I think this is something that we would add to our practice."
This study was supported by Dermik Laboratories. Dr. Stough reported receiving support for travel to the ASDS meeting. Dr. Weiss disclosed no relevant financial relationships.
American Society for Dermatologic Surgery (ASDS) 2008 Annual Meeting: Poster 17. Presented November 7, 2008.
Medscape Medical News © 2008 Medscape
Cite this: Deborah Brauser. ASDS 2008: Fluorouracil Cream 0.5% Reduces Actinic Keratoses on Multiple Body Sites - Medscape - Nov 10, 2008.
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