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 © December 2012
George J. Schmieder DO,a Eugene Y. Huang MD PhD,b and Michael Jarratt MDc
aPark Avenue Dermatology, Orange Park, FL bTherapeutics Clinical Research, San Diego, CA cDermResearch, Inc, Austin, TX
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.
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-
