Study of Methyl Aminolaevulinate Photodynamic Therapy With and Without Er:YAG Laser in Bowen's Disease

July 30, 2013 updated by: Song Ki-Hoon, Dong-A University

A Randomized, Intra-individual, Prospective Study Comparing Methyl Aminolaevulinate Photodynamic Therapy With and Without Er:YAG Ablative Fractional Laser Treatment in Asian Patients With Lower Extremity Bowen's Disease

Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is an effective treatment for Bowen's disease (BD) of the lower extremities. Er:YAG ablative fractional laser (AFL) treatment removes the stratum corneum to increase MAL uptake and may improve efficacy. However, no studies have directly compared the efficacy of MAL-PDT with and without Er:YAG AFL in treating BD of the lower extremities in Asians.

Study Overview

Status

Completed

Conditions

Detailed Description

Bowen's disease (BD) is a form of intraepidermal (in situ) squamous cell carcinoma (SCC) originally described in 1912.1 It presents as a gradually enlarging, well-demarcated erythematous plaque with an irregular border and surface crusting or scaling.2 BD is the frequent precancerous skin lesion in Caucasians.3 In the UK, BD occurrence is most common among patients in their 70s and in women (70-85%), and the majority (60-85%) of cases involve lesions of the lower leg.4,5 BD is estimated to evolve into invasive SCC in 3-5% of cases; therefore, treatment is recommended.6 Current guidelines suggest that the available therapeutic options (including cryotherapy, curettage, excision, topical 5-fluorouracil, and topical imiquimod) are broadly similar in efficacy, with 12-month recurrence rates of approximately 5-10%.7 However, cryotherapy can be painful, making treatment of multiple lesions difficult, and healing can be slow.8 Additionally, topical treatment with 5-fluorouracil or imiquimod is relatively slow and typically causes local irritation.9,10 Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an attractive treatment option for BD with large or multiple patches, and poor healing sites can be treated with good efficacy, low recurrence rates, and good cosmetic outcomes.7 PDT requires light activation of a photosensitizer in the presence of oxygen, which generates reactive oxygen species leading to selective and highly localized destruction of abnormal cells.11,12 MAL is an efficient photosensitizer, with deep lesion penetration resulting from enhanced lipophilicity. Compared to 5-aminolevulinic acid, MAL also has a greater specificity for neoplastic cells.13-15 Because histologic features of BD include full-thickness keratinocyte atypia with disordered maturation, it is typically treated twice within an interval of 1 week.16,17 So, complementary techniques are needed to enhance the penetration and accumulation of MAL in order to improve PDT efficacy and decrease treatment duration.

Er:YAG ablative fractional laser therapy (AFL) can ablate the stratum corneum in a precisely tuned manner without producing significant thermal injury. This approach creates microscopic vertical holes in the ablated tissue, surrounded by thin layers of coagulated tissue.18,19 Since the Er:YAG AFL resurfaces 5-20% of the skin at one time and does not injure the entire thickness of the epidermis, healing times are minimized.18,19 Recent studies have demonstrated that AFL facilitates delivery and uptake of topical MAL deep into the skin, enhancing porphyrin synthesis and photodynamic activation.20,21 The objectives of this study were to compare the efficacy, recurrence rate, cosmetic outcomes, and safety of MAL-PDT with and without the use of Er:YAG AFL in Asian BD patients with multiple lower extremity lesions.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Dong dae sin-dong, Seo-gu
      • Busan, Dong dae sin-dong, Seo-gu, Korea, Republic of, 602-715
        • Dong-A University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Korean patients aged ≥ 18 years who had biopsy-confirmed BD lesions on the lower extremities

Exclusion Criteria:

  • porphyria,
  • known allergies to the MAL cream or lidocaine,
  • pregnancy,
  • lactation,
  • any active systemic infectious disease,
  • immunosuppressive treatment,
  • personal history of malignant melanoma,
  • tendency towards melasma or keloid formation,
  • prior treatment of the lesions within 4 weeks, and
  • any indication of poor compliance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Er:YAG AFL-PDT
Right leg on each patients was assigned a single session of Er:YAG AFL-PDT.
Er:YAG AFL was performed with 550-600 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. MAL cream was then applied under occlusion for 3 hrs and illuminated with a red light-emitting diode light at 37 J/cm2.
Other Names:
  • Er:YAG ablative fractional laser-assisted MAL-PDT
Active Comparator: MAL-PDT
Left leg on each patient was selected to receive 2 sessions of MAL-PDT
a 1-mm thick layer of MAL (16% Metvix® cream, PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, Saint Paul, MN, US) for 3 hours, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Each treatment area was then separately illuminated with red light-emitting diode (LED) lamps (Aktilite CL128; Galderma, Bruchsal, Germany) with peak emission at 632 nm and total light dose of 37 J cm-2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later.
Other Names:
  • methyl aminolaevulinate-Photodynamic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference the efficacy between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT.
Time Frame: Efficacy was evaluated at 3 months and 12 months after treatment
Lesion response was classified as either complete (complete disappearance of the lesion) or incomplete (incomplete disappearance) on the basis of visual examination and palpation. The response of each lesion was clinically evaluated
Efficacy was evaluated at 3 months and 12 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference of the cosmetic outcomes between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT.
Time Frame: Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 3 or 12 months
It 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 3 or 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference of the recurrence rates and safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT.
Time Frame: within 12 months after both treatment

If the case of complete response of lesions, all patients were reviewed at 12 months to check recurrence.

Adverse events reported by the patient 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 (i.e. erythema, postinflammatory hyperpigmentation, oedema, itching, oozing, bleeding, etc.).

within 12 months after both treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Ki-Hoon Song, M.D., Ph.D., Assistant professor and Chariman, Department of dermatology Dong-A University, College of medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

July 9, 2013

First Submitted That Met QC Criteria

July 29, 2013

First Posted (Estimate)

July 31, 2013

Study Record Updates

Last Update Posted (Estimate)

August 1, 2013

Last Update Submitted That Met QC Criteria

July 30, 2013

Last Verified

July 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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