Photodynamic therapy uses broaden as more data emerges

Miami Beach, Fla. - Physicians have greatly changed the ways in which they use photodynamic therapy (PDT) since it was introduced, according to an expert who spoke at the South Beach Symposium recently.

Since earning Food and Drug Administration (FDA) approval in 1999, PDT with aminolevulinic acid (ALA) has evolved to encompass off-label uses including treatment of actinic keratoses (AKs) on the hands and arms, superficial nonmelanoma skin cancers in nonsurgical candidates and actinic cheilitis (AC), says Joel L. Cohen, M.D., director of AboutSkin Dermatology in Englewood and Lone Tree, Colo., and associate clinical professor at the University of Colorado department of dermatology.

“People are using phototherapy in many new and exciting ways. In my practice, I use PDT from a medical, surgical and cosmetic perspective,” he says.

Although the FDA approved PDT for application to specific areas, Dr. Cohen says, “Broad application is now pretty standard.”

Extremity application

Similarly, methods for enhancing ALA penetration on the extremities include vigorous preparation of the skin, sometimes including application of topical retinoids such as tazarotene. In this regard, a 10-patient study showed that pretreatment with tazarotene gel 0.1 percent twice daily for one week before ALA PDT with blue light resulted in a statistically significant decline in lesion counts versus baseline eight weeks post-treatment (p=0.0002; Galitzer BI. J Drugs Dermatol. 2011;10(10):1124-1132).

Other methods to enhance ALA penetration on the arms and hands include the addition of occlusion and heat during the incubation period, Dr. Cohen says. In Europe, he adds, physicians commonly use PDT (albeit usually a different formulation no longer available in the United States - Metvix; methyl aminolevulinate, Galderma) for very superficial basal cell carcinoma (BCC; Matei C, Tampa M, Poteca T, et al. J Med Life. 2013;6(1):50-54) and squamous cell carcinoma (SCC) in situ.

Dr. Cohen says he often uses PDT for patients with superficial nonmelanoma skin cancers (NMSC) who are poor surgical candidates due to age or other reasons (inability to care for a wound, or patient on chemotherapy). For example, “Such a patient may specifically have SCC in situ. If the base of the biopsy specimen is visualized, and there’s no concern about any invasive component and no evidence of significant follicular extension, I may use PDT,” he says.

Such cases require disclosing to the patient and/or patient’s family that the treatment is not FDA-approved for this indication, but it may be appropriate in the case at hand, he says.

“In some cases, we’ll gently scrape the skin with a curette to create a minor abrasion to enhance topical penetration if the lesion is a bit keratotic, then apply the Levulan (DUSA Pharmaceuticals) ALA under occlusion (using Saran Wrap, S.C. Johnson & Son; or Glad Press’n Seal, Glad Products). Usually with a couple treatments, one will see a response. And that may be preferable because the patient can go back to a nursing home without any woundcare requirements,” Dr. Cohen says. “This would not be the case if the patient had undergone electrodesiccation and curettage, as this treatment would necessitate at least some woundcare.”

Actinic cheilitis treatment

For AC, he adds, “One can apply the ALA to the lower lip and activate it with a pulsed dye laser (Alexiades-Armenakas MR, Geronemus RG. J Drugs Dermatol. 2004;3(5):548-551) or blue light (Zaiac M, Clement A. J Drugs Dermatol. 2011;10(11):1240-1245). A couple treatment sessions can yield significant improvement.”

In the latter study, investigators gave 15 patients with clinically evident or biopsy-proven AC two treatments, spaced three to five weeks apart, with ALA PDT using blue light activation. Three to five weeks after the first treatment, most patients achieved 65 to 75 percent clearance. All patients achieved more than 75 percent clearance one month after the second treatment, and three patients achieved complete clearance.

However, Dr. Cohen is quick to point out that for more severe cases of AC, he prefers to perform an ablative laser vermillionectomy - which can often be one treatment, and depth can be determined based on number of laser passes (Cohen JL. J Drugs Dermatol. 2013;12(11):1290-1292).

Along with medical applications, Dr. Cohen says, he and other dermatologists commonly use PDT in combination with intense pulsed light (IPL) and other light-based devices for aesthetic purposes. Many studies, including several split-face comparisons, have shown that this combination provides increased improvement in fine lines, wrinkles and pigmentation versus IPL alone (Alster TS, Tanzi EL, Welsh EC. J Drugs Dermatol. 2005;4(1):35-38), he says.

“And sometimes physicians use microdermabrasion or even a light erbium peel, or a fractional laser, to enhance penetration when patients are undergoing PDT for cosmetic use,” Dr. Cohen says.

Likewise, studies have shown that dermal rollers - applied to the skin before ALA - may improve PDT results. In one study, puncturing excised murine skin with arrays of microneedles 270 µm long, spaced 750 µm apart, led to significant increases in transdermal delivery of ALA released from a bioadhesive patch (Donnelly RF, Morrow DI, McCarron PA, et al. J Control Release. 2008;129(3):154-162).

Disclosures: Dr. Cohen is a consultant for DUSA Pharmaceuticals.