Medical management of NMSCs

Kohala Coast, HI

- Despite the way some trivialize dermatologists’ management of skin conditions ("Dermatology? Just stick some aloe on it and move on"), there exist many serious and potentially complicated treatment protocols for the management of cutaneous diseases.

This is particularly true with the medical management of nonmelanoma skin cancers (NMSCs), said Neal Bhatia, M.D., at the Winter Clinical Dermatology Conference.

According to Dr. Bhatia, medical management of these cancers is especially important for the elderly (those who may be on coumadin, oxygen, and/or live in hospice or nursing homes); for patients who have a high risk for recurrence; for those reluctant to biopsy/surgery; and for those with immunosuppressed systems.

Other issues surrounding the medical management of NMSCs include the question of whether medical therapy can be used after surgery to decrease the risk of recurrence, as well as whether the HPV vaccine can be used for effective chemoprevention.

Currently, Dr. Bhatia says, we have sunscreens, retinoids, 5-FU and imiquimod available for the medical management of NMSCs. Down the road, dermatologists can expect to see curcumin, lycopene, T4 endonuclease, cox-2 inhibitors, DFMO and polyphenolic antioxidants added to this armamentarium.

Chemopreventive agents currently in clinical trials include oral retinoids (isotretioin, acitretin, etretinate), T4 endonuclease and genistein cream, which protects human skin from UVB-induced erythema when applied topically. Genistein removes damaging free radicals and reduces lipid peroxidation while increasing the activity of other antioxidant enzymes and influencing the growth of cells that are not hormone-dependent. No adverse events have been reported with the use of genistein to date, said Dr. Bhatia, an associate clinical professor at the University of Wisconsin Medical School.

Dr. Bhatia also outlined the general progression of carcinogenesis. "This is not from the sun patients got yesterday … this is an investment," he said, adding that sunscreens should most definitely be used in an individual’s 20s to prevent the process from ever occurring.

Ultraviolet (UV) penetration causing P53 mutation and then resulting in subclinical actinic keratoses (AKs) is the stage at which immune response modifiers can serve to modify the process of subclinical disease, thus reducing the progression to advanced mutation. Once UV penetration results in ras mutation and subsequently clinical AKs, antimetabolites such as 5-FU can be used to rapidly divide the epithelium affected by mutations, Dr. Bhatia said.

Retinoids should take effect just before UV rays result in P16 mutation and then squamous cell carcinoma by maintaining epidermal maturation and differentiation, he added. This is the mutation that must be prevented to avoid invasive skin disease.

Ultimately, immunosuppression occurs as a consequence of years of unprotected UV exposure. ŎSun-damaged skin is immunosupressed," Dr. Bhatia explained. "This is basically leukopenic skin."

Dr. Bhatia also discussed tazarotene 0.1 percent gel for superficial basal cell carcinomas (sBCCs). This drug can remodel the papillary and reticular dermis and regulate gene transcription. As for imiquimod and 5-FU, "these are two distinct concepts," he said, citing that imiquimod induces inflammation, while with 5-FU, inflammation is secondary.

For tumor suppressor genes mutated by UV exposure, the topical chemoprevention agent Cyclopamine (veratrum alkaloid) has been shown to achieve rapid regression of skin tumors in mice, as well as tumor cell inhibition and aptosis, Dr. Bhatia said. For topical remodeling and repair mechanisms, Dimericine cream can repair DNA (similar to imiquimod), particularly for immunosuppressed patients.

Regarding final rules for medical management, Dr. Bhatia advised that dermatologists maximize combination approaches. The benefits of chemoprevention outweigh the risks, he said, and most importantly, doctors should always do what is best for the patient at the time. DT