Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial.

BACKGROUND: No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis. OBJECTIVE: To determine the 6-month outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery. DESIGN: Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical trial performed in community and academic outpatient clinics. PATIENTS: A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face. INTERVENTIONS: Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the 4-week follow-up visit, residual lesions were treated with cryosurgery. MAIN OUTCOME MEASURE: Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months. RESULTS: At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5% fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months, mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001). CONCLUSIONS: A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly more effective in reducing patients' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone. The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up.

Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.

The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.

A novel 0.5% fluorouracil cream is minimally absorbed into the systemic circulation yet is as effective as 5% fluorouracil cream.

Recent in vitro and in vivo studies compared the absorption of a 0.5% fluorouracil cream with that of a 5% fluorouracil cream, following topical application to the skin. Both studies demonstrated that fluorouracil is minimally absorbed into the systemic circulation. Despite a one-tenth concentration difference between formulations, the cumulative amount of fluorouracil excreted in the urine of patients treated with the 0.5% cream was one fortieth that of patients treated with the 5% cream. Interestingly, higher percentages of fluorouracil were retained in the skin following application of the 0.5% cream compared with the 5% cream, suggesting that delivery of the 0.5% cream may be more targeted to the affected area. Other studies have demonstrated that the 0.5% cream is as effective as the 5% cream for the treatment of actinic keratoses (AKs) and has a more favorable tolerability profile. Therefore, this new 0.5% fluorouracil cream may be a safer, yet equally effective treatment alternative.

Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.

New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.

BACKGROUND: A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available. OBJECTIVE: This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK). METHODS: During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events. RESULTS: Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation. CONCLUSIONS: In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent reduction in AK lesions and total clearance of AK lesions; it was more effective than the 5% cream in reducing the absolute number of AK lesions from baseline. Patients preferred the 0.5% cream to the 5% cream.