Instead of the traditional 16 weeks of therapy, the 3.75% cream is used daily for 2 weeks, followed by a 2-week rest, then another 2 weeks of therapy, for a total 6-week treatment course. And the imiquimod 3.75% cream is approved for treatment of the full face or balding scalp, unlike imiquimod 5%, whose approved indication is limited to a much smaller area of 25 cm2, Dr. Rosen said.
In the pivotal trial for imiquimod 3.75%, 160 treated patients showed a complete clearance rate of 35.6% and a median 81.8% reduction in AKs 8 weeks after the final treatment. That is near-identical to the 83.3% reduction noted in an earlier trial of 215 patients treated with imiquimod 5%.
Dr. Rosen said field therapy makes sound sense in patients with multiple AKs in the same area of the skin.
"When you have a patient with [a lot of] AKs, then all the skin in between those AKs is no more normal than the AK skin; it just hasn’t manifest yet. That’s where field therapy comes in," he explained.
As much as he likes field therapy, though, Dr. Rosen stressed that the emerging new paradigm for treatment of patients with multiple AKs is combination therapy. This can take the form of either a field therapy followed by individual lesion-directed therapy such as cryotherapy, or lesion-directed therapy followed by a field therapy. There are numerous possible combinations. Insurance reimbursement can be a problem for now, but payers will eventually have to come around to the new paradigm.
"The bottom line is for every study where field therapy is combined with lesion-directed therapy or with another field therapy, the combination proved superior to monotherapy," Dr. Rosen said. "It's a little more work, but in the end I think it's probably the best thing for your patient."
Other Agents in the AK Pipeline
AK remains an active target for new drug development. Among the wide range of drugs in the developmental pipeline, albeit still years away from the marketplace, are:
Resiquimod and sotirimod. These are the most promising of the more than 1,000 known analogues of imiquimod. Like the parent compound, they work via immune upregulation, said Dr. Rosen.
Betulin. A triterpene isolated from the extract of birch bark. It eliminates actinic keratoses through cytotoxicity.
Perillyl alcohol. A monoterpene isolated from essential oils of peppermint, spearmint, lavender, and other plants. Its mechanism of action involves induction of apoptosis in rapidly dividing cells without affecting normal cells.
Difluoromethylornithine. Irreversibly inhibits ornithine decarboxylase, which regulates cell division. DFMO is already marketed in a topical formulation for the treatment of facial hirsutism, and as an injectable drug for treatment of African trypanosomiasis.
Afamelanotide. This synthetic analogue of melanocyte-stimulating hormone is under development as a treatment for a diverse collection of skin diseases, including polymorphous light eruption, solar urticaria, and squamous cell carcinoma, as well as AKs.
T4 endonuclease V. This drug enhances repair of UV-induced DNA damage. "It might help prevent future AKs, but not existing ones," Dr. Rosen said.
Why does AK therapy remain such a busy area of new drug development? Simple: A substantial portion of the public continues to be casual about sun protection or disregards it altogether, and with the graying of the baby boomer generation, AKs are more common than ever, he said.
"Everybody in Texas has AKs, including me. I just found one on my hand, and now I need to go treat it," he said.
Dr. Rosen is on the speaker's bureau for Graceway and is a consultant to Graceway and Leo Pharmaceuticals. SDEF and this news organization are owned by Elsevier.