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

NCT ID: NCT01912976

Last Updated: 2013-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-03-31

Brief Summary

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.

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.

Conditions

Bowen's Disease

Keywords

Bowen's disease; Er:YAG; AFL-assisted; MAL-PDT

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Er:YAG AFL-PDT

Right leg on each patients was assigned a single session of Er:YAG AFL-PDT.

Group Type: EXPERIMENTAL

Er:YAG AFL-PDT

Intervention Type: DRUG

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.

MAL-PDT

Left leg on each patient was selected to receive 2 sessions of MAL-PDT

Group Type: ACTIVE_COMPARATOR

MAL-PDT

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Er:YAG ablative fractional laser-assisted MAL-PDT; methyl aminolaevulinate-Photodynamic therapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 92 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dong-A University

OTHER

Sponsor Role: lead

Responsible Party

Song Ki-Hoon

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ki-Hoon Song, M.D., Ph.D.

Role: STUDY_CHAIR

Assistant professor and Chariman, Department of dermatology Dong-A University, College of medicine

Locations

Dong-A University

Busan, Dong Dae Sin-dong, Seo-gu, South Korea

Countries

South Korea

Other Identifiers

DAUDerma-01

Identifier Type: -

Identifier Source: org_study_id