Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease

Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease: A Prospective, Randomized, Controlled Trial With 5-year Follow up

Er:YAG ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-PDT) has shown significantly higher efficacy and a lower recurrence rate at 12 months than methyl aminolevulinate photodynamic therapy (MAL-PDT) for treatment of Bowen's disease (BD). However, long-term follow up data are not available.

Study Overview

• Status: Completed
• Conditions: Bowen's Disease
• Intervention / Treatment: Drug: lidocaine-prilocaine 5% cream application; Device: 2940-nm Er:YAG AFL pretreatment; Drug: methyl-aminolevulinate application; Device: Illuminating using red light-emitting diode lamps

Detailed Description

To compare the long-term efficacy and recurrence rates of AFL-PDT and standard MAL-PDT for the treatment of lower extremity BD.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 42 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• •Patients aged 18 years or more who diagnosed as bowen's disease

Exclusion Criteria:

• pregnancy or lactation
• active systemic infectious disease
• other inflammatory, infectious, or neoplastic skin diseases in the treated area
• allergy to MAL,other topical photosensitizers, or excipients of the cream
• history of photosensitivity
• use of immunosuppressive or photosensitizing drugs
• participation in any other investigational study in the preceding 30 days
• history or indicators of poor compliance
• Histological findings of acantholysis, desmoplasia, perineural or lymphovascular invasion, and echographic features of regional lymph node metastasis were the disease-specific exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MAL-PDT; Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT or MAL-PDT	Drug: methyl-aminolevulinate application; Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.; Device: Illuminating using red light-emitting diode lamps; Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.
Experimental: AFL-PDT; Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT or MAL-PDT	Drug: lidocaine-prilocaine 5% cream application; The lesions were then cleansed with saline gauze, and a lidocaine-prilocaine 5% cream (EMLA®; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area for 30 min under occlusion; Device: 2940-nm Er:YAG AFL pretreatment; After the anesthetic cream was removed, AFL was performed using a 2940-nm Er:YAG AFL (Joule; Sciton, Inc., Palo Alto, CA, USA) with a 500 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse; Drug: methyl-aminolevulinate application; Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.; Device: Illuminating using red light-emitting diode lamps; Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of short-term complete response (CR) rate between AFL-PDT and MAL-PDT	The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)	Short-term CR rate was evaluated at 3 months
Difference of long-term complete response (CR) rate between AFL-PDT and MAL-PDT	The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)	Long-term CR rate was evaluated at 60 months
Difference of long-term recurrence rate between AFL-PDT and MAL-PDT at 60 months	In all cases of complete response, the patients were reviewed at 60 months to check for recurrence. Post-therapy punch biopsies were performed when there was doubt concerning incomplete-response and clinical recurrence	Recurrent rate was evaluated at 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of the cosmetic outcome between AFL-PDT and MAL-PDT	The overall cosmetic outcome was assessed by each investigator for all lesions that achieved complete response at 60 months, and was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight to moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)	Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of Adverse events(erythema, burning sensation, swelling, bleeding) between AFL-PDT and MAL-PDT	Adverse events reported by the patients were noted at each follow-up visit, including severity, duration, and need for additional therapy. All events due to PDT were described as phototoxic reactions(e.g erythema, burning sensation, swelling, bleeding)	Within 60 months after each treatment

Collaborators and Investigators

• Sponsor: Dong-A University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2011
• Primary Completion (Actual): October 30, 2016
• Study Completion (Actual): October 19, 2017

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 23, 2017
• First Posted (Actual): October 25, 2017

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: photodynamic therapy; ablative fractional laser; protoporphyrin IX; methy-aminolevulinate
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Bowen's Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Photosensitizing Agents; Dermatologic Agents; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anesthetics, Combined; Lidocaine; Aminolevulinic Acid; Prilocaine; Lidocaine, Prilocaine Drug Combination; Methyl 5-aminolevulinate
• Other Study ID Numbers: DAUderma-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No