Las Vegas — Topical imiquimod field treatment addresses not only visible and subclinical actinic keratoses (AKs), but it also appears to provide greater long-term clearance than does liquid nitrogen cryotherapy, an expert says.

Researchers believe the toll-like receptor agonist imiquimod (Aldara, Graceway) works by augmenting both the innate and acquired immune arms of immunologic response, says James Q. Del Rosso, D.O., dermatology residency director, Valley Hospital Medical Center, Las Vegas.

Basically, the drug facilitates and amplifies the immunologic response of its host, Dr. Del Rosso says.

Because imiquimod possesses no direct cytotoxic properties, successful therapy requires antigen recognition followed by a functional host immune response.

That being the case, Dr. Del Rosso asks, "Could potential immunologic memory serve to reduce the development of recurrent or new AKs in the field treated with topical imiquimod?"

To answer this question, Dr. Del Rosso and Sanjay Bhambri, D.O., chief dermatology resident at Valley Hospital Medical Center, Las Vegas, reviewed 12-month follow-up data from a recently published randomized trial that compared clinical and histologic outcomes after treatment of AKs with topical imiquimod, topical 5-fluorouracil (5-FU) or cryotherapy (Krawtchenko N, Rowert M, Ulrich I et al. Br J Dermatol. 2007:157(Suppl 2):34-40.)

The study included 75 Caucasian patients with five to 10 AKs within an anatomic region measuring up to 50 cm2 on the head, neck or chest.

Researchers randomized patients to receive either liquid nitrogen cryotherapy, topical 5-FU five percent cream or topical imiquimod 5 percent cream. They used grids and clinical photographs to track the location of initially treated AKs.

Additionally, they took a 4 mm punch biopsy specimen at baseline from a representative AK lesion for histologic assessment.

Investigators took another skin biopsy from either a cleared focus, if present, or the most suspicious-looking persistent lesion, from each patient at the end of therapy (EOT).

They defined EOT as six weeks after the last cryotherapy application, four weeks after the last dose of topical 5-FU, or eight weeks after the last dose of topical imiquimod.

At EOT, researchers observed complete clinical clearance in 96 percent of patients treated with topical 5-FU, 85 percent of those treated with topical imiquimod, and 68 percent of those treated with cryotherapy.

As for histologic clearance, however, imiquimod achieved this endpoint in 73 percent of treated patients, compared to 67 percent of those treated with 5-FU and 32 percent of patients treated with cryotherapy.

Additionally, patients were assessed 12 months after EOT to determine whether or not initially treated AKs had recurred or if new AKs developed in the field of treatment.

At this point, they observed complete clearance in 86 percent of subjects who had initially been cleared with topical imiquimod, versus 57 percent of those treated with 5-FU and 41 percent of cryotherapy-treated patients (p <0.01).

Similarly, among all patients — including those not completely cleared at EOT — investigators observed complete clearance of initially treated lesions in 73 percent of imiquimod-treated patients, 54 percent of those treated with 5-FU, and 28 percent of those treated with cryotherapy.

"One benefit of topical therapy for AKs, particularly compared to ablative therapies that target individual lesions, is treatment of subclinical AKs through field application," Dr. Del Rosso tells Dermatology Times.

It's important to note that 12 months post-treatment, researchers saw sustained field clearance in only 4 percent of cryotherapy-treated patients, as compared to 33 percent of those treated with 5-FU, and 73 percent of those treated with topical imiquimod (p <0 .01), he adds.

"It makes sense to use cryotherapy for a more immediate ablative effect for individual visible AKs, and use topical therapy through field application to further augment clearance of currently visible lesions and to also eradicate subclinical AKs that have not yet emerged," Dr. Del Rosso says.

In this study, topical imiquimod outperformed the other two treatments in terms of long-term cosmetic outcomes.

In this regard, investigators observed no significant differences in cosmetic outcomes between the three treatments at EOT.

After 12 months' follow-up, however, they rated cosmetic outcomes as excellent in 81 percent of imiquimod-treated patients, versus four percent in both the cryotherapy and 5-FU cohorts.

Although cryotherapy remains an important tool for managing currently visible lesions, Dr. Del Rosso says, "It fails to address subclinical lesions within the affected regions."

In contrast, he says that topical imiquimod, using the cycle therapy approach, has been shown to provide greater clearance one year after treatment for both currently visible lesions and for AKs within the entire treatment field than either cryotherapy or topical 5-FU based on currently available data.

"The differing mechanisms of action among the therapies may account for differences that may be observed with regard to clinical response — particularly delayed clearance," he says. DT

Disclosures: Dr. Del Rosso is a researcher, consultant and/or speaker for Allergan, Coria, Galderma, Graceway, Intendis, Medicis, Onset Therapeutics, OrthoNeutrogena, Pharmaderm, Quinnova, Ranbaxy, SkinMedica, Stiefel, Unilever and Warner Chilcott.

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