WINSTON-SALEM, N.C., Feb. 22 /PRNewswire/ -- Conclusions of a 12-month clinical trial announced at the 63rd American Academy of Dermatology Annual Meeting this past weekend indicate that a one-week course of treatment with the topical 0.5% fluorouracil cream Carac(R) before cryosurgery is significantly more effective in reducing actinic keratosis (AK) lesions than cryosurgery alone.
"Although cryosurgery is the most commonly used treatment for the removal of AKs, most patients will develop many new lesions after six months," said the study's lead author, Joseph Jorizzo, MD, professor, former and founding chair of the department of dermatology, Wake Forest University School of Medicine, Winston-Salem, NC. "This study demonstrated that a one week course of treatment with Carac(R) prior to cryosurgery significantly increases the number of patients who are clear of facial AK lesions at six and twelve months."
The study, sponsored by Dermik Laboratories, is the first randomized, controlled trial to evaluate the long-term outcome of cryosurgery and the effect of a regimen using Carac(R) before cryosurgery. The 142 patients were randomly assigned to apply topical 0.5% fluorouracil cream or placebo once daily for seven days to the face plus one or more investigator-designated areas, including the scalp, ears, neck and/or lips. Residual AKs were treated with liquid nitrogen cryosurgery after four weeks and patient evaluations were made six and twelve months later.
Researchers found that greater reductions in AK lesions on the face and overall occurred after 1, 2, and 3 cycles of a 1-week course of treatment with topical 0.5% fluorouracil before cryosurgery than with cryosurgery alone. The greatest reduction in AK lesions and greatest proportion of patients with clearance of AK lesions occurred after 2 cycles of a 1-week course of fluorouracil before cryosurgery than with cryosurgery alone.
While the benefit of fluorouracil 0.5% prior to cryosurgery was demonstrated in each of the study's three treatment cycles, the highest percentage of patients with total clearance of facial AK lesions was recorded in cycle two at six months.
After four weeks of treatment with either fluorouracil 0.5% or placebo, mean AK lesion count was reduced by 62.4 percent in the 0.5% fluorouracil group compared to 28.8 percent in the placebo group (p<.001), with complete clearance being achieved in 16.7 percent of patients receiving 0.5% fluorouracil versus zero percent for those on placebo (p<.001).
More patients remained clear of AK lesions 6 months after the first cycle of a 1-week course of topical 0.5% fluorouracil before cryosurgery than those who received cryosurgery alone. Six months following cryosurgery, mean lesion count of residual AKs was reduced by 67 percent in the 0.5% fluorouracil plus cryosurgery group compared to 45.6 percent in the placebo plus cryosurgery group (p=.011). Additionally, significantly more patients in the 0.5% fluorouracil plus cryosurgery group achieved complete clearance (30 percent vs. 7.7 percent; p<.001). Total clearance of AK lesions was not maintained at 12 months after initial treatment.
"The data underscore the need to evaluate patients 6 and 12 months after treatment for AKs, especially if cryosurgery alone is used," concluded Jorizzo.
Treatment with 0.5% fluorouracil was generally safe and well tolerated. The most common adverse events seen were eye irritation (14.1% placebo vs. 13.9% fluorouracil cream) and application site reactions (4% placebo vs. 18% fluorouracil cream). No patient discontinuations due to adverse events were reported.
AKs are very common, pre-cancerous lesions that arise on photo-damaged skin resulting from exposure to ultraviolet (UV) radiation, the primary source of which is sunlight. An estimated forty-six million Americans will develop an AK during their lifetime. AKs contain individual cells with all the characteristics of squamous cell carcinoma. Up to 20% of untreated AK lesions progress into invasive squamous cell carcinoma, the second most common form of skin cancer. Because AK has the potential to evolve into an aggressive disease, treatment of all AK lesions has been recommended by the American Academy of Dermatology.
Effective treatments for AK include chemical destruction by topical medications such as 5-fluorouracil or physical destruction by cryosurgery, curettage, electrosurgery, and in limited cases, excision or dermabrasion. The most commonly used treatment modality in the United States is cryosurgery with liquid nitrogen. Clinical trials repeatedly have found topical fluorouracil to be effective for the treatment of AK lesions when applied in concentrations of 0.5%, 1% or 5%. "Destructive treatments such as cryosurgery are limited by their inability to destroy pre-cancerous AK lesions. Field treatments such as 5FU, imiquimod and diclofenac are not able to destroy hypertrophic (thick) lesions because of their inability to penetrate into the lesion. Thus the need for this combination data," said Jorizzo.
About Carac(R) (fluorouracil cream) Cream, 0.5%
Carac(R) (fluorouracil cream) Cream, 0.5% is a once-a-day, topical treatment for actinic keratosis of the face and anterior scalp that has been approved by the U.S. Food and Drug Administration. Carac(R) provides patients with an effective AK treatment with the benefit of convenient once-a-day dosing. It is marketed by Dermik Laboratories, the North American Dermatology unit of sanofi-aventis.
About Wake Forest University School of Medicine
Wake Forest University School of Medicine is a unit of Wake Forest Baptist, an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences. The system comprises 1,298 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.
Wake Forest University School of MedicineCONTACT: Joseph Jorizzo, MD of Wake Forest School of Medicine,+1-336-716-2768; or Peter Collins of Rowland Communications Worldwide,+1-212-527-8847, Peter.Collins@Rowland.com