Novel strategies minimize actinic keratoses treatment burdens

Wailea, Hawaii - Field therapy in patients with multiple facial actinic keratoses (AKs) is important for preventing the development of new, clinically visible lesions and squamous cell carcinoma. Yet, for a number of reasons, including the need for prolonged topical treatment and poor tolerability, field therapy is widely underused.

Speaking at the MauiDerm 2014 meeting, George M. Martin, M.D., private practice, Kihei, Hawaii, and MauiDerm program director, discussed various on-label, combination, and off-label approaches for increasing the acceptability of field therapy.

Topical treatments

When using topical 5-fluorouracil (5-FU), Dr. Martin has patients apply the 0.5 percent cream (Carac, Medicis) once daily for just seven days (face) or 10 days (nonfacial skin). Treatment response is evaluated after a one-month rest period, and topical 5-FU is resumed for two to three weeks if needed to treat residual lesions.

Use of this regimen is on-label, as it is based on results from two phase-3 studies in which patients using the 0.5 percent 5-FU cream for just one week achieved a lesion clearance rate of about 75 percent. Comparator arms treated for two or four weeks achieved lesion clearance rates of about 85 and 90 percent, respectively, and experienced significantly more irritation.

“A continuous four-week course of topical 5-FU is a brutal regimen that should be abandoned because the increased downtime it causes is not worth the extra efficacy gained over one week of therapy,” Dr. Martin says. “In my experience, using a second cycle of treatment as a clean-up phase provides the same efficacy results and is well-tolerated.”

As a regimen to minimize downtime for patients using imiquimod 3.75 percent cream (Zyclara, Medicis) for field treatment, Dr. Martin prescribes once daily application for seven days, a two-week rest period, and then resumes treatment just once a week. He acknowledges there is no evidence-based efficacy data to support this approach. Dr. Martin says, however, he has had good results with it in clinical practice.

In addition, investigators conducting a published split-face, placebo-controlled study reported once weekly treatment with imiquimod 5 percent cream resulted in significant improvement and was well-tolerated (Zeichner JA, et al. J Am Acad Dermatol. 2009;60(1):59-62).

“We should be thinking about patients with multiple AKs as having a chronic disease, and with that concept in mind, I can’t think of a better strategy than to use an immunomodulator for long-term suppression,” Dr. Martin says.

“Patients must still be counseled about local adverse reactions after the initial course of daily treatment. The severity of the response is proportional to the degree of the actinic damage, but patients should expect about seven days of downtime following cessation of the initial one week of daily therapy,” he says.

Ingenol mebutate 0.015 percent gel (Picato, Leo Pharma) applied nightly for three nights has proven to be highly effective treatment for patients with multiple AKs on the face and scalp. However, according to the prescribing information, the treatment area should not exceed 25 cm². Dr. Martin notes that a study evaluating a 250 cm² treatment area with ingenol 0.015 percent is underway. However, he has been treating some patients in this manner with good results. 

Results with PDT

Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA; Levulan Kerastick, DUSA Pharmaceuticals) performed per the prescribing information with a 14 to 18 hour incubation time is highly effective as field therapy, but also inconvenient. Short-contact PDT using an incubation time of only one to three hours is more practical, but also less effective, unless the patient undergoes two treatment sessions eight weeks apart.

Alternatively, Dr. Martin says the efficacy of a single, short-contact PDT session (one hour incubation time) can be increased by pretreating patients with 5-FU 0.5 percent cream (seven days to the face, 10 days to the scalp) or imiquimod 3.75 percent cream for seven days in patients with refractory facial AKs.

In addition, Dr. Martin says he is finding that PDT can be performed with minimal to no pain using a regimen that involves a 15-minute 5-ALA incubation time and exposure to blue light (BLU-U, DUSA) for one hour.

“I have used this technique for ‘painless’ PDT with good results in about 40 patients, both as monotherapy and in patients pretreated with a topical agent. However, formal studies quantifying clearance rates of ‘painless PDT’ as monotherapy are warranted to verify my experience,” Dr. Martin says.

Disclosures: Dr. Martin is a consultant, speaker, and/or scientific advisory board member for companies marketing products used in the treatment of AKs.