PDT May Have a Future in Chemoprevention

LAS VEGAS — Chemoprevention with photodynamic therapy is encouraging—the therapy increases the time it takes actinic keratoses to develop into skin cancer, according to anecdotal data and preliminary results of larger trials.

Chemoprevention is the most important indication for photodynamic therapy (PDT), Dr. Michael H. Gold said at an international symposium on cosmetic and laser surgery.

Initial reports indicate efficacy for basal cell carcinoma, especially superficial lesions, and researchers have reported improvements to nodular basal cell and ulcerative basal cell lesions.

"PDT is wonderful for basal cell carcinoma on the ear. Mohs surgeons don't want to touch it, and my only other option is radiation," said Dr. Gold, who is in private practice in Nashville, Tenn., and is also with Vanderbilt University, Nashville.

Methyl-aminolevulinic HCl (Metvixia/PhotoCure, Galderma) and 5-aminolevulinic acid (ALA) (Levulan Kerastick, Dusa Pharmaceuticals) are the two photosensitizers generally studied for use with photodynamic therapy. Dr. Gold is a researcher, speaker, and consultant for Dusa.

ALA is approved for the treatment of precancerous actinic keratoses on the face and scalp. The product is being developed for the treatment of acne and photodamage, according to the manufacturer's Web site. Methyl-aminolevulinic HCl (methyl-ALA) is approved in the United States for treatment of nonhyperkeratotic actinic keratoses. The product is marketed in Europe as Metvix and carries an additional indication for basal cell carcinoma unsuitable for conventional therapy.

"What is interesting is what has been done with Metvix," Dr. Gold said. There has been a great deal of "very good work done in Europe with Metvix for actinic keratoses and Bowen's disease. It is now the treatment of choice in Europe for Bowen's disease."

There are two very interesting studies in Europe looking at immunosuppressed organ transplant patients treated with methyl-ALA, Dr. Gold said.

In one study, a single treatment with methyl-ALA/PDT delayed development of actinic keratoses for 9.6 months, versus 6.8 months in untreated patients (Acta. Derm. Venereol. 2006;86:25–8). The second study is an ongoing multicenter trial with 81 transplant patients enrolled to date who were treated with either methyl-ALA/PDT or cryotherapy. There was a significantly lower number of actinic keratoses in the areas treated with methyl-ALA/PDT, according to preliminary findings presented at the 10th World Congress on Cancers of the Skin in Vienna in 2005.

European research includes reports of two patients who had an allergic contact dermatitis reaction to methyl-ALA but not ALA (Br. J. Dermatol. 2004;150:143–5). "So keep this in mind in the United States," Dr. Gold said.

In a study of 69 patients with multiple actinic keratoses on their faces, patients receiving PDT with methyl-ALA reported less pain on a 0–10 scale compared with a PDT/ALA combination (J. Drugs Dermatol. 2006;5:353–6).

A second investigation compared PDT with ALA or methyl-ALA for inflammatory acne vulgaris (J. Am. Acad. Dermatol. 2006;54:647–51). This split-face study with 15 participants found no differences in response rates but more prolonged and severe adverse effects on the ALA-treated side. The treatment protocol was not a fair comparison, Dr. Gold said, which "is important to understand. The authors stated the ALA side will give you as much, if not more, adverse events than the methyl-ALA. But you cannot compare apples to oranges as they did this in the study.

"My response to both of these articles is, basically, you cannot compare short-term application of ALA, where we have no problems, to long-term methyl-ALA under occlusion, where we have problems," Dr. Gold said.