A Multicenter, Randomized, Vehicle-Controlled Phase 2 Study of Blue Light Photodynamic Therapy With Aminolevulinic Acid HCl 20% Topical Solution for the Treatment of Actinic Keratoses on the Upper Extremities: The Effect of Occlusion During the Drug Incubation Period

December 2012 | Volume 11 | Issue 12 | Original Article | 1483 | Copyright © 2012

George J. Schmieder DO,a Eugene Y. Huang MD PhD,b and Michael Jarratt MDc

Abstract

Background: Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been shown to be safe and effective in the treatment of actinic keratoses (AKs) of the face and scalp. A recent small study has suggested that ALA-PDT can be effective for AKs of the dorsal hands/forearms. However, studies designed to provide sufficient statistical power to test this hypothesis are lacking in the literature.
Objectives: To determine and compare the safety and ef!cacy of blue light ALA-PDT vs blue light placebo vehicle (VEH) in the treatment of AKs of the upper extremities and to evaluate the effect of occlusion after application of ALA vs VEH.
Methods: ALA or VEH was applied to both dorsal hands/forearms for the 3-hour incubation period before blue light treatment (10 J/ cm2). One extremity of each subject was covered with occlusive dressing during the incubation period. Treatment was repeated at week 8 if any AK lesions remained.
Results: The median AK lesion clearance rate at week 12 was 88.7% for extremities treated with occluded ALA (ALA+OCC), 70.0% for extremities treated with nonoccluded ALA, 16.7% for extremities treated with occluded VEH (VEH+OCC), and 5.6% for extremities treated with nonoccluded VEH (P<.0001). ALA+OCC resulted in a significantly higher clearance rate compared with the nonoccluded extremity at weeks 8 (P=.0006) and 12 (P=.0029). Thirty-four percent (12/35) of extremities treated with ALA+OCC had complete clearance of lesions at week 12 compared with 0% (0/35) of extremities treated with VEH+OCC (P=.0002). The safety pro!le in this study is consistent with previously reported side effects of the therapy.
Conclusion: Blue light ALA-PDT following a 3-hour incubation appears efficacious for AK clearance of the upper extremities. Incubation using an occlusive dressing significantly increases the efficacy of the procedure and also increases the incidence and severity of some acute inflammatory side effects of PDT.

J Drugs Dermatol. 2012;11(12):1483-1489.

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INTRODUCTION

Actinic keratoses (AKs) are common dysplastic epidermal lesions that occur in fair-skinned individuals who have been chronically exposed to sunlight. Actinic keratosis lesions are usually found on sun-exposed areas such as the face, bald scalp, forearms, and backs of the hands. Individual AKs are identified clinically as scaly, rough, skin color to red, pinpoint to larger patch lesions that may disappear and reappear over months or years. Actinic keratoses are considered to be precancerous lesions with the potential to progress to squamous cell carcinoma (SCC). The results of a recent study suggest that AKs may give rise to nonmelanoma skin cancers at a greater rate than previously acknowledged.1 Criscione et al1 found that the risk of progression of AK to primary SCC was 0.6% at 1 year and 2.57% at 4 years; in addition, during the trial, approximately 65% of all primary SCCs diagnosed in the study population arose in lesions that had earlier been clinically diagnosed as AKs. The cellular damage and atypia seen at the histologic level of AKs is similar to that of surrounding nonlesional skin,2,3 suggesting that the skin surrounding AK lesions may also be at increased risk of skin cancer.

Photodynamic therapy (PDT) with application of a 20% topical solution of aminolevulinic acid (ALA) HCl (Levulan Kerastick; DUSA Pharmaceuticals, Inc, Wilmington, MA) and activation by 10 J/cm2 blue light (BLU-U Blue Light Photodynamic Therapy Illuminator; DUSA Pharmaceuticals, Inc) exposure is approved by the US Food and Drug Administration for the spot treatment of minimally to moderately thick AK of the face or scalp after a 14- to 18-hour incubation period in the United States, and is also approved in Canada, Brazil, Mexico, Argentina, and Korea.

When ALA is applied to dysplastic lesions, it is absorbed by cells and preferentially metabolized to the highly potent photo-

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