Actinic Keratoses (gr I-III) clinical trials

Treating Actinic Keratoses With Natural Daylight PDT: Comparing Two Light Sensitizers (ALA and MAL)

Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metasthatic 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 sensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells. The approved photosensitizers in Europe are methylaminolevulenic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulenic acid (5-ALA, Alacare®, Spirig AG) and aminolevulenic 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 policlinical sensitizer absorption and illumination. At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). Ameluz® holds a lower unit price and it's clearance rate compares to Metvix™ in LED-PDT. We are piloting a study comparing the cost-efficacy of these two light sensitizers in NDL-PDT. Our hypothesis is that there will be at least 0,30 difference in the histopathological curing of the lesions. Our other hypothesis is that Ameluz® with it's lower unit price results in reduced treatment costs and better cost-efficacy compared to Metvix™. The efficacy of the treatments will be assessed clinically, histopathologically, immunohistochemically and by hyper spectrum camera imaging.