A Randomized Trial of Broad Area ALA-PDT for Field Cancerization Mitigation in High-Risk Patients.

BACKGROUND: The relationship between actinic keratoses (AKs) and nonmelanoma skin cancers (NMSCs) is well established. Patients with field cancerization are at high risk of developing new lesions. A treatment to interrupt new lesion formation or progression is required. OBJECTIVE: To evaluate occurrence of AKs in high-risk patients after field aminolevulinic acid–photodynamic therapy (ALA–PDT). METHODS: In this randomized, parallel-group, evaluator-blinded, 52-week study, patients with 4–15 facial AKs (N = 166) were random-ized (ALA 2x vs ALA 3x vs vehicle [VEH]-pooled [VEH 2x+VEH 3x], 1:1:1) to receive 2 or 3 PDT treatments (1-hour incubation) following cryotherapy at screening. RESULTS: More ALA-treated patients than VEH-treated patients had no AKs at week 52 (ALA 2x, 36.0%, P=0.0102; ALA 3x, 37.5%, P=0.0089; VEH, 18.9%). Week 52 lesion recurrence rates were 7.7% (P=0.0004) and 6.1% (P<0.0001) for ALA 2x and ALA 3x, respec-tively, versus 15.5% for VEH. Therapy was well tolerated; no patient requested early termination of light treatment. ALA 3x reduced NMSC development versus VEH (5 vs 12 lesions, P=0.0014). CONCLUSION: 2 or 3 ALA–PDT treatments with 1-hour incubation can significantly reduce occurrence of AKs after 1 year in patients at high risk of NMSC versus VEH–PDT (NCT02239679). J Drugs Dermatol. 2020;19(5):452-458. doi:10.36849/JDD.2020.4930.

A Randomized, Vehicle-Controlled Phase 3 Study of Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses on the Upper Extremities.

BACKGROUND: Blue-light aminolevulinic acid photodynamic therapy (ALA-PDT) after broad-area application and 3-hour incubation is efficacious for actinic keratosis (AK) lesion clearance on upper extremities, with use of occlusive dressing significantly increasing efficacy. OBJECTIVE: To prove the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the spot treatment of multiple AKs on upper extremities. METHODS: Aminolevulinic acid or VEH was spot applied only to lesions on one upper extremity 3 hours before blue-light exposure. Treated extremity was covered with occlusive dressing during incubation. Identical treatment was repeated at Week 8 if AK lesions were present in the treated area. RESULTS: Thirty-one percent (42/135) of subjects treated with ALA-PDT had complete clearance at Week 12, compared with 13% (17/134) of the subjects treated with VEH-PDT (p = .0001). The mean AK lesion clearance rate for ALA-treated subjects at Weeks 8 and 12 was 53% and 69%, respectively, compared with 26% and 30% for the VEH-treated group (p < .0001, linear mixed model). Safety profile observed in this study is consistent with previous studies/reports in the literature, and the therapy was well tolerated overall. CONCLUSION: Aminolevulinic acid-PDT spot treatment using a 3-hour occluded incubation was superior to VEH-PDT for AK lesion clearance of the upper extremity.

Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp.

BACKGROUND: Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. OBJECTIVE: To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. METHODS: Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. RESULTS: Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. CONCLUSION: Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.

Efficacy of aminolevulinic acid 20 % solution photodynamic therapy in the treatment of actinic keratoses on the upper extremities: A post hoc analysis of a phase 3, randomized, vehicle-controlled trial.

BACKGROUND: Photodynamic therapy with 5-aminolevulinic acid is indicated for targeted treatment of actinic keratoses on the face, scalp, and upper extremities. This was a post hoc analysis of a phase 3 randomized trial assessing the efficacy of aminolevulinic acid/photodynamic therapy for treatment of actinic keratoses on the upper extremities. METHODS: Adults with 4-15 grade 1-2 actinic keratosis lesions on ≥1 upper extremity were randomized (1:1) to receive aminolevulinic acid/photodynamic therapy or vehicle/photodynamic therapy applied to individual lesions followed by occlusion and blue light treatment. Assessments included the clearance rate of treated lesions vs baseline, cumulative disease area clearance, and complete clearance by lesion size. RESULTS: There were 135 and 134 patients randomized to aminolevulinic acid/photodynamic therapy and vehicle/photodynamic therapy groups, respectively. At 12 weeks, clearance of treated lesions (80.6 % vs 45.5 %; P <0.0001) and the mean decrease in cumulative disease area (82.4 % vs 42.6 %; P <0.0001) was significantly higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy, respectively. Rates of complete clearance and clearance by cutpoint (≥90 %, ≥85 %, ≥80 %, or ≥75 % clearance) were numerically higher for aminolevulinic acid/photodynamic therapy. Clearance of lesions was higher for aminolevulinic acid/photodynamic therapy vs vehicle/photodynamic therapy regardless of baseline lesion size. Aminolevulinic acid/photodynamic therapy was well tolerated with adverse events consistent with those expected with photodynamic therapy. CONCLUSIONS: Aminolevulinic acid photodynamic therapy is effective and well tolerated for the treatment of actinic keratosis lesions of the extremities.