Actinic keratosis, NMSC treatments benefit from innovative approaches

February 1, 2012

Future management of actinic keratosis (AK) and nonmelanoma skin cancer (NMSC) will involve creative uses of conventional therapies, particularly in multimodal regimens, and it will be expanded by recent advances in chemotherapy, according to Theodore Rosen, M.D., who spoke at the 30th annual Fall Clinical Dermatology Conference.

Key Points

Las Vegas - Future management of actinic keratosis (AK) and nonmelanoma skin cancer (NMSC) will involve creative uses of conventional therapies, particularly in multimodal regimens, and it will be expanded by recent advances in chemotherapy, according to Theodore Rosen, M.D., who spoke at the 30th annual Fall Clinical Dermatology Conference.

"Remember that when treating AKs and NMSCs, no one size fits all, and thanks to recent developments, our patients are benefiting with broadened options to meet the spectrum represented by their individual needs," says Dr. Rosen, professor of dermatology, Baylor College of Medicine, Houston.

For patients who present with multiple AKs in a cosmetic unit, treatment of the entire photodamaged area with field-directed therapy rather than lesion-specific treatment is appropriate. When considering topical field therapy for AKs, physicians may expect to have a new lower concentration of imiquimod available in the future, as imiquimod 2.5 percent cream (Zyclara, Medicis) was approved by the Food and Drug Administration in July 2011 for treatment of AKs, Dr. Rosen says.

Dr. Rosen says results from controlled clinical trials suggest that when it comes to topical imiquimod treatment of AKs, less can be more. Both the currently available 3.75 percent formulation and the new 2.5 percent product provide initial and one-year clearance rates that compare favorably with imiquimod 5 percent, albeit slightly lower, but with the above-mentioned advantages as well as better tolerability, he says.

"With the lower concentrations of imiquimod, dermatologists will have a whole library of products that will allow us to tailor our therapy to the patient's tolerance," Dr. Rosen says.

Multimodal mindset

Treatment of AKs in the future will also involve an increased emphasis on multimodal therapy using a combination of field-directed and lesion-directed options or two field therapies, according to Dr. Rosen. These approaches have been investigated using a variety of different modalities, and as a bottom line, results from controlled studies have demonstrated that initial clearance rates and durability of response is superior using the combined approach compared with monotherapy.

"There are cost and insurance issues to consider, but it is clear from the available evidence that multimodal therapy is probably the best thing to do for patients who have multiple AKs," Dr. Rosen says.

NMSC advancements

Reviewing some therapies for NMSCs that may not be high on the radar screen for some dermatologists, Dr. Rosen reminded Fall Clinical attendees that topical imiquimod 5 percent can be very effective in off-label use for treating large superficial basal cell carcinomas (sBCC), as reported in a recent publication (Lacarrubba F, Potenza MC, Gurgone S, Micali G. J Dermatolog Treat. 2011;22(6):353-358) and a much earlier paper by Dr. Rosen and colleagues (Chen TM, Rosen T, Orengo I. Dermatol Surg. 2002;28(4):344-346).

However, patients should be counseled about developing a severe local reaction, and prescribers should be prepared to offer some hand-holding in the middle of the therapeutic course, he says.

Fractional cryosurgery offers another novel approach that may be considered for treating large BCCs or squamous cell carcinomas (SCCs). Reported by a Portuguese dermatologist (Almeida Gonçalves JC. G Ital Dermatol Venereol. 2011;146(4):249-255; Almeida Gonçalves JC. Dermatol Surg. 2009;35(11):1788-1796) who used the technique to treat cancers greater than 10 mm on both the head/neck and extremities, it employs a series of cryosurgery sessions in which the lesion is frozen hard in the center to produce progression contraction until lesion diameter has shrunk to a size where it can be frozen with attainment of an adequate margin, Dr. Rosen says.

"The freeze technique is not standardized, two to four treatments were needed, and there is a scar. However, this can be a procedure to consider in patients who do not want surgery or are not good candidates for surgery," Dr. Rosen says.

Although radiation therapy is an often-overlooked modality for NMSCs, there has been a renaissance of interest in the use of brachytherapy in Europe in particular, Dr. Rosen says. In this technique where the radiation is applied directly onto the lesion with a tightly focused beam, underlying structures are protected, which makes it a good choice for treating the back of the hand and scalp. In addition, the procedure is generally well-tolerated, and the cosmetic results are "excellent," he says.

"As described in a recent review article (Alam M, Nanda S, Mittal BB, et al. J Am Acad Dermatol. 2011;65(2):377-388), efficacy is excellent, although the best results are achieved when treating smaller, superficial, thinner tumors. Radiation therapy is something not used much for NMSCs anymore, but it is something to keep in mind and makes it worth knowing a radiation therapist for patient referrals," Dr. Rosen says.

Local advancement

For patients with locally advanced NMSC, medical oncologists are now having success using targeted systemic chemotherapeutic agents. For example, in a phase 2 study including 36 patients with advanced unresectable SCC (Maubec E, Petrow P, Scheer-Senyarich I, et al. J Clin Oncol. 2011;29(25):3419-3426), first-line monotherapy with cetuximab (Erbitux, Lilly/Bristol-Myers Squibb), an epidermal growth factor receptor inhibitor, either stopped tumor growth or shrunk the tumor in 70 percent of patients and made surgical resection feasible for some tumors.

"These chemotherapy drugs are well-tolerated, except for causing an acneiform eruption that is treatable and actually signals a good prognosis. So keep them in mind as possible options," Dr. Rosen says.

On the horizon, ingenol mebutate 0.05 percent gel (LEO Pharma) could gain FDA approval for the treatment of multiple AKs, Dr. Rosen says. Results for both complete clearance and median lesion reduction were favorable in pivotal trials investigating treatment of lesions on the head and neck or the extremities using a regimen of once-daily application for just two or three days. Recently released one-year follow-up data also looks very good, he says.

Promising results are also being reported for treatment of locally advanced or metastatic BCC using vismodegib (Roche), an oral, small-molecule Hedgehog pathway inhibitor, and it is also under FDA review.

Disclosures: Dr. Rosen has received honoraria as a consultant and speakers bureau member for Graceway. He is a consultant to LEO Pharma.