Current Methods for Photodynamic Therapy in the US: Comparison of MAL/PDT and ALA/PDT
August 2013 | Volume 12 | Issue 8 | Original Article | 925 | Copyright © 2013
aPeter K. Lee MD PhD and bAndrew Kloser PhD
aUniversity of Minnesota Medical Center, Minneapolis, MN
bGalderma Laboratories LP, Lantana, TX
There is some debate regarding the rate of progression of actinic keratosis (AK) into squamous cell carcinoma (SCC).1-4 However, it is clear that treatment for AK lesions is warranted. Results from numerous studies with aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) for the treatment of AKs, SCC, and Bowen's disease show high rates of clearance for these lesions. MAL/PDT provides similar efficacy to ALA/PDT with the benefits of shorter incubation times according to the approved FDA labeling, greater selectivity, reduced pain during and immediately following therapy, and fewer systemic side effects. Cosmetic outcomes are better with PDT than with cryosurgery or excisional surgery. A number of case reports show efficacy with ALA/PDT and MAL/PDT for acne, photorejuvenation, and other off-label indications. Side effects with PDT tend to be mild to moderate and transient in nature. Overall, ALA/PDT and MAL/PDT are effective for a variety of skin diseases and conditions. MAL/PDT provides some advantages over ALA/PDT.
J Drugs Dermatol. 2013;12(8):925-930.
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Photodynamic therapy (PDT) has been a relatively late addition to the treatment modalities available to the dermatologist.5 This review will provide a survey of recent preclinical and clinical data that are available for two agents, aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), that are currently available in the US for use with PDT. The two compounds will be compared in order to provide the clinician with practical information on the utility of each agent for his or her clinical practice setting. The focus of the article will be the information surrounding these two agents for the treatment of actinic keratoses (AKs) but other uses will also be described. It should be noted that currently these additional uses are considered to be off-label in the US.
Photodynamic therapy is based on the interaction of light, oxygen, and a photosensitizer.6 The photosensitizer is applied either topically or systemically, typically as a prodrug or metabolic precursor of the active agent. The photosensitizer is activated via illumination with visible light. The energy is then transferred to oxygen molecules by a Type II photo-oxidation reaction, and reactive oxygen species (ROS) are generated. Cell death occurs by way of the reaction of singlet oxygen with cell membranes and organelles. The choice of an appropriate light source is key to ensure photosensitizer excitation and tissue penetration.7 PDT has proved to be quite effective for the treatment of AKs. MAL and ALA are chemically distinct protoporphyrin IX (PpIX) precursors that are enzymatically converted to PpIX, an active photosensitizer.
The Prevalence of Actinic Keratosis
Actinic keratosis prevalence is relatively high due to the etiology of this disease. Depending upon the population studied and the geographic location, the prevalence of AK may be as high as 60%.8-12 Gupta et al evaluated the National Ambulatory Medical Care Survey (NAMCS) data from 1990 to 1999. In over 47 million visits during this 10-year period, AKs were diagnosed in 14% of the patients who visited a dermatologist.13 These data actually do not reflect the true prevalence of the disease since only patients seeking a physician’s diagnosis were included. The key risk factors in the development of AK include sun exposure, working outdoors, fair skin, history of sunburn, advancing age, and immunosuppression.14
It is important to treat AK lesions since many progress to squamous cell carcinoma (SCC).2,15 In a study of 1689 participants, Marks et al found that 60% of SCCs arose from lesions that had been diagnosed as AK.3 A separate trial conducted on 169 participants with 7784 AKs showed that 65% of SCCs arose from lesions that had previously been diagnosed as AK.1 The study also found the risk of progression from AK to SCC to be 0.60% at 1 year and 2.57% at 4 years. In another study, it was reported that the annual incidence of SCC in people with multiple AKs was about 0.24% for each kerotosis.16 These findings were later extrapolated to estimate that a person with eight AKs would have a 6-10% risk of developing SCC over a 10-year period.2 In a study by Fuchs and colleagues, 10% of AKs developed into SCCs, and the progressions took approximately 2 years.17 These findings underscore the need to treat AK lesions proactively.
Aminolevulinic acid (Levulan Kerastick®, DUSA Pharmaceuticals Inc, Wilmington, MA) with blue light PDT is approved for the treatment of AKs in the US, Korea, Mexico, Brazil, Argentina, Chile, and Columbia.18,19 Each treatment applicator contains one