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What's old is new again for actinic keratoses treatment.

EXPERT ANALYSIS FROM THE AAD ANNUAL MEETING

DENVER -- Changes in health insurance coverage are prompting a resurgence in the use of 5-fluorouracil to treat actinic keratoses, said Dr. Linda Susan Marcus.

Not only is 5-fluorouracil (5-FU) effective, "but it has become increasingly difficult to get some of the newer topical agents covered by health insurance plans, especially Medicare. This is the reality now," she said at the annual meeting of the American Academy of Dermatology.

Dr. Marcus, a dermatologist in Wyckoff, N.J., noted that 5FU blocks methylation of de acid in DNA, altering only fast-dividing cancerous cells. The agent is available in 1%, 2%, and 5% solutions, and in 1% and 5% creams. "We don't really use the solutions much anymore; they're very irritating," she said, noting that the 5% cream is really the gold standard. Her approach is to have patients apply the 5% 5-FU cream to the affected area twice a day for 3 weeks. Another option is a 0.5% 5-FU cream with a microsphere delivery system "that traps the active ingredients in the skin surface to increase efficacy and decrease irritation," she said. "Some people use this for maintenance or cycle therapy prior to cryosurgery."

As for side effects, 5-FU elicits erythema, scaliness, and crusting (which can be avoided with the milder preparations); but these reactions are selflimited, she noted.

Other topical preparations for actinic keratoses on the market include:

* Diclofenac sodium 3% in 2.5% hyaluronic acid gel. This colorless agent is designed to be applied twice a day for 2-3 months. "That can pose a compliance issue for some patients," Dr. Marcus said. "The mechanism is unknown, but it probably functions as an NSAID that may involve prostaglandin levels in UV-exposed skin and upregulation of COX-2, which may promote proliferation. Cyclooxygenase is the ratelimiting enzyme step in prostaglandin synthesis."

Dr. Marcus said that diclofenac sodium 3% in 2.5% hyaluronic acid gel may be best suited for patients with mild lesions and for pre- or post cryosurgery.

* Imiquimod. A 5% formulation of imiquimod "is becoming the new gold standard of topical therapies, but it can be irritating," Dr. Marcus said. A 3.75% formulation is available that is designed to be used for 2 weeks, followed by a 2-week break, and then the patient repeats the cycle, Dr. Marcus said, adding that she uses the 3.75% formulation most often for her patients with actinic keratoses. She described imiquimod as an immune response modifier that induces mRNA encoding cytokines like alphainterferon, TNF, and interleukin-12 for a cytotoxic T-lymphocyte response.

Dermatologists often tweak the frequency of application, she added, and results from some studies suggest that outcomes with imiquimod are similar to those obtained with 5-FU, while others hint that imiquimod may provide longer-lasting results. "Field-directed therapy is the advantage since it brings out subclinical lesions, but you need a lot of hand holding to encourage patients with this phenomenon," Dr. Marcus said.

* Ingenol mebutate (PEP005). Approved as a gel in January of 2012, ingenol mebutate is a natural diterpene from the Euphorbia peplus flowering plant in Southeast Asia. The agent is believed to augment neutrophil-killing ability on abnormal cells via damaging mitochondria, and its antiangiogenic properties promote healing and skin regeneration. "It's proven histologically in superficial basal cell epithelioma, which is interesting, because this drug is approved only in the United States and the indication is only for actinic keratosis and not for superficial basal cells," Dr. Marcus said.

Dr. Marcus disclosed that she has financial relationships with numerous pharmaceutical companies.

dbrunk@frontlinemedcom.com

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Title Annotation:DERMATOLOGY
Author:Brunk, Doug
Publication:Family Practice News
Geographic Code:1USA
Date:Apr 15, 2014
Words:602
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