Actinic keratoses

Kohala Coast, HI

- Because there are multiple effective modalities that can be used for the treatment of actinic keratoses (AKs), clinicians should consider both the overall goal(s) they want to achieve and recent developments in therapeutic approaches, said Roger I. Ceilley, M.D., while speaking at the Winter Clinical Dermatology Conference.

"The primary aim of treating AKs is to prevent squamous cell carcinoma (SCC) invasion and metastasis, but other objectives can include reducing the likelihood of new lesions and proactively treating subclinical lesions," said Dr. Ceilley, clinical professor of dermatology, University of Iowa, Iowa City.

Cryosurgery with liquid nitrogen remains the workhorse in many practices, but there is emerging information about the enhanced value of combination/sequential therapy as well as medical therapy with imiquimod (Aldara, Graceway). In addition, a new form of photodynamic therapy (PDT) was recently approved by the FDA.

Discussing combination treatment, Dr. Ceilley cited a study reporting the benefits of using 5-fluorouracil cream 0.5 percent with cryotherapy. Analysis of AK lesion reduction at 6 months showed a significant difference, favoring patients who used the medical treatment for one week prior to ablative therapy versus those having pretreatment with a placebo cream.

Similarly, another recently published study shows that sequential treatment with cryosurgery followed by diclofenac sodium 3 percent gel for 90 days provides improved outcomes compared with cryosurgery alone. In the latter study, rates of 100 percent cumulative lesion clearance and target lesion clearance were significantly higher in the sequential treatment arm.

"Destructive methods for AK treatment get only the tip of the iceberg. They do not induce any favorable immunologic changes nor have any field effect," he said.

PDT for AKs using methylaminolevulinate (MAL) 16.8 percent cream (Metvixia, Galderma) and red light was recently approved by the FDA, although it has not been launched commercially. With two treatments administered two weeks apart using a regimen involving a 3-hour occlusion period for the photosensitizing agent and 10 minutes of exposure to 75 J/cm2 red light, the AK resolution rate was 89 percent.

Results of a multicenter study comparing MAL PDT with cryosurgery for patients with multiple AKs on the extremities found the percent-lesion reduction rate was 10 percent higher with cryosurgery, but the cosmetic outcome and patient preference ratings favored the PDT approach.

Alternative dosing regimens for imiquimod is an important development, since the 16-week application period evaluated in the pivotal clinical trials is too long to be practical. Instead, clinicians should be flexible and look for clues to identify a therapeutic endpoint.

"If the lesions become edematous, erythematous and erosive, they are probably doomed to die. Treating longer will cause discomfort and can increase the risk for hypopigmentation without improving efficacy," Dr. Ceilley said.

Published literature from comparative studies of imiquimod, cryosurgery and 5-fluorouracil also indicates that imiquimod provides the best results in terms of the endpoints of complete clearing, sustained clearance and cosmetic outcomes. DT