Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01912976
Recruitment Status : Completed
First Posted : July 31, 2013
Last Update Posted : August 1, 2013
Information provided by (Responsible Party):
Song Ki-Hoon, Dong-A University

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.

Condition or disease Intervention/treatment Phase
Bowen's Disease Drug: Er:YAG AFL-PDT Drug: MAL-PDT Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2011
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

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 Name: 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 Name: methyl aminolaevulinate-Photodynamic therapy

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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)

Other Outcome Measures:
  1. 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.).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 92 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01912976

Layout table for location information
Korea, Republic of
Dong-A University
Busan, Dong dae sin-dong, Seo-gu, Korea, Republic of, 602-715
Sponsors and Collaborators
Dong-A University
Layout table for investigator information
Study Chair: Ki-Hoon Song, M.D., Ph.D. Assistant professor and Chariman, Department of dermatology Dong-A University, College of medicine
Layout table for additonal information
Responsible Party: Song Ki-Hoon, Assistant professor, Dong-A University Identifier: NCT01912976    
Other Study ID Numbers: DAUDerma-01
First Posted: July 31, 2013    Key Record Dates
Last Update Posted: August 1, 2013
Last Verified: July 2013
Keywords provided by Song Ki-Hoon, Dong-A University:
Bowen's disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Bowen's Disease
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Methyl 5-aminolevulinate
Photosensitizing Agents
Dermatologic Agents