Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Dermatologic Agents

All Drugs and Chemicals

Anti-Infective Agents

Central Nervous System Depressants

Aminolevulinic Acid

Ethanol

Methyl 5-aminolevulinate

Photosensitizing Agents

BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then sun protection factor (SPF) 20 cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz cream on the area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

BF-200 ALA cream

The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Metvix cream on the area. After appropriate absorption time of 30 minutes, the patientswill be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.

MAL cream

Noora E Neittaanmäki-Perttu, MD

Toni T Karppinen, MD

Taneli Tani, PhD

The aim of the study is to compare the efficacy of two photosensitizers, methyl-aminolaevulinate (MAL) and 5-aminolaevulinic nanoemulsion (BF-200 ALA) in the treatment of facial actinic keratosis. We use randomized, double-blinded prospective study design. The efficacy will be assessed clinically, histopathologically and immunohistochemically.

Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metastatic squamous cell carcinoma. AKs can be treated with photodynamic therapy (PDT), of which cure rate compares to cryo surgery with an excellent cosmesis. In PDT the AK lesions are first curettaged, then a photosensitizer is applied on the skin and let to absorb for 3 hours. The skin is illuminated using a blue or red light source light source depending on the photosensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells.

The approved photosensitizers in Europe are methyl-aminolevulinic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulinic acid (5-ALA, Alacare®, Spirig AG) and 5-aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG) to be used with a red LED light (630-635 nm). In North America a 5-aminolevulinic acid stick (5-ALA, Levulan® Kerastick) can also be used with a blue light source (417 nm).

PpIX absorption peaks are within the visual spectrum of light, which allows PpIX daylight activation. During natural daylight PDT (NDL-PDT) protocol, PpIX is continuously activated during its development, whereas in conventional PDT (LED-PDT) using red LED lamps, large amounts of accumulated PpIX are momentarily activated.

Since skin field cancerization refers to presence of different degrees of visible and invisible dysplastic changes, the whole area should be treated to prevent the development of non-melanoma skin cancers (NMSCs). NDL-PDT enables treatment of field cancerization in one sitting whereas LED-PDT may need repeated illuminations to cover the whole area. NDL-PDT results in enhanced cost-efficacy due to reduced staff expenses, since there's no need for sensitizer absorption and illumination.

At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). We are piloting a study comparing the efficacy of these two light sensitizers in NDL-PDT. The efficacy of the treatments will be assessed clinically, histopathologically and immunohistochemically.

Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)

Treatment of AKs With Daylight-PDT: Comparing Two Photosensitizers (BF-200 ALA and MAL)

Adverse reactions are evaluated by blinded observer at one week after treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction.

Punch biopsies were taken symmetrically on both treatment fields from equally graded \>6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (\<10 % normal)

Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m.

(treatment day). Of these values, the mean maximal pain is assessed.

Clinical lesion clearance is observed by a blinded observer

Joint Authority for Päijät-Häme Social and Health Care

BF-200 ALA (Ameluz, Biofrontera) and MAL (Metvix, Galderma) in randomized slipt face design on symmetrical treatment areas.

BF200 ALA vs MAL

BF-200 ALA vs MAL

Age, Continuous

Sex: Female, Male

Number of AKs

14 patients were recruited. One withdrew because of conditions not related to the study. This patient was not included in the analysis.

Noora Neittaanmäki-Perttu

BF-200 ALA

BF-200 ALA (Ameluz, Biofrontera) and MAL (Metvix, Galderma) in randomized split face design on symmetrical treatment areas.

Punch biopsies bilaterally on treatment fields

Histological Lesion Clearance

BF-200 ALA treatment sides

MAL treatment sides

Pain

BF-200 ALA treated lesions

MAL treated lesions

Clinical Lesion Clearance

BF-200 ALA treated areas

MAL treated areas

No difference between the sides

One week after the first photodynamic therapy (PDT), seven patients had more severe reactions (erythema, crusting) at the site treated with BF-200 ALA, five patients had more severe reactions at the MAL site and one patient showed no difference between sites.

Adverse Reactions

5-aminulevulinic acid nanoemulsion (BF-200 ALA, Ameluz, Biofrontera) and methylaminolevulinic acid (MAL, Metvix, Galderma) in randomized split face design on symmetrical treatment areas.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)	NCT01893203	Multiple Actini...	BF-200 ALA crea... MAL cream	18 Years -	Joint Authority for Päijät-Häme Social and Health Care
Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)	NCT01893203	Multiple Actini...	BF-200 ALA crea... MAL cream	18 Years -	Joint Authority for Päijät-Häme Social and Health Care

Spots Global Cancer Trial Database for multiple actinic keratoses