Hexyl-5-aminolaevulinate 0·2% vs. methyl-5-aminolaevulinate 16% daylight photodynamic therapy for treatment of actinic keratoses: results of a randomized double-blinded pilot trial

Neittaanmäki-Perttu, Noora; Grönroos, Mari; Karppinen, Toni; Tani, Taneli; Snellman, Erna

doi:10.1111/bjd.13924

Cited by 14 publications

(10 citation statements)

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“…Longer chain ALA esters, such as hexyl-ALA (C6), display a higher PpIX yield, but as they are more lipophilic, they are taken up via passive diffusion and may result in lower selectivity toward neoplastic cells [60,61]. While MAL and ALA have been approved for topical treatment of AK and basal cell carcinoma, only few studies exist that investigate the use of hexyl-ALA for epidermal neoplasms [62]. Another approach to circumvent the short half-life of ALA in solution is the immediate preparation before use, as in a two-chamber applicator device containing ALA and alcohol to produce a 20% ALA solution [63].…”

Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 99%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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BF-200 ALA is a combination of a nanoscale-lipid vesicle formulation and the prodrug 5-aminolevulinic acid (5-ALA). The nanoemulsion stabilizes the prodrug and enhances its penetration through the stratum corneum. It has shown excellent therapeutic results in both lesion and field-directed photodynamic therapy of actinic keratosis (AK). AK is an early form of epidermal neoplasia and a precursor of invasive cutaneous squamous cell carcinoma. It is characterized by the combination of visible neoplastic lesions and surrounding tissue also harboring tumorigenic UV-induced mutations: a concept called field cancerization. A selective, field-directed treatment is ideal to meet the requirements of field change. Here, we review the clinical data on BF-200 ALA for AK along with a summary of molecular mechanisms and future perspectives. Actinic keratosis (AK), also known as solar keratosis, is caused by chronic exposure to sunlight or other ultraviolet light sources [1,2] and may progress to invasive squamous cell carcinoma (SCC) [3]. It is the most common lesion with malignant potential to arise on the skin. AK is mostly seen in Caucasians in skin areas that have extensive sun exposure throughout their lives [4]. Epidemiological data show a high occurrence rate of AK. Regions with higher ultraviolet exposure have a higher prevalence of AK. For the USA, the prevalence was estimated to range from 11 to 26%, while in Australia it ranged from 40 to 60%. In Europe, a prevalence of 15% in men and 6% in women has been documented [5]. Over the age of 70 years, 34% of men and 18% of women were found to have actinic keratotic lesions [6]. Next to fair skin type, an advanced age and lifelong sun exposure immunosuppression/-deficiency plays another important risk factor [5].Mostly, AK develops slowly and early in the disease process, they may disappear only to reappear later. Recurrence of the disease may include partial elimination of the initial lesion, subclinical lesion progression to visible status, or development of new lesions [7]. On top of this, an AK may progress to invasive SCC, the second-most common form of skin cancer [8,9]. The actual percentage of progress to invasive SCC remains unknown, and estimates vary from 5 to 20% within 10 to 25 years with reported annual transformation rates varying greatly from as low as 0.25% to as high as 16% [10]. The regression rate for a single untreated lesion is 15 to 63% after a year; recurrence rates range from 15 to 53% [11]. In general patients develop multiple AKs in one area and predicting which course each individual lesion will follow is impossible. Nonetheless, AK lesions are reliable markers for patients who are most predisposed to developing invasive SCC [4,[12][13].AK lesions typically appear in areas most frequently exposed to the sun such as the face, back of the hands, or bald scalp; 75% of lesions are found on the head, neck and forearms [14]. The lesions vary in appearance as well as size and can include erythematous scaly macules, rough pigmented patches and hyperker...

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Section: Enhancing Pdt With Nanoemulsion Technologymentioning

confidence: 99%

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis

Reinhold¹

2017

Future Oncol.

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“…The potential of low dose lipophilic Hexyl-5-aminolaevulinate (HAL) 0.2% to provide deeper penetration was investigated in comparison to MAL-PDT in a randomised pilot study. Comparable results were found for mild AKs, but HAL was less effective for moderate to severe lesions [96]. Better uptake and targeting of photosensitisers may be achieved in the future, using novel delivery systems such as nanoparticles, micelles or liposomes [95].…”

Section: Future Directionsmentioning

confidence: 99%

Photodynamic Therapy and Non-Melanoma Skin Cancer

Griffin

Lear

2016

Cancers

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Non-melanoma skin cancer (NMSC) is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT) is gaining popularity for the treatment of basal cell carcinoma (BCC), Bowen’s disease (BD) and actinic keratosis (AK). A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX) is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate) PDT for AKs has the advantage of decreased pain and better patient tolerance. PDT is an effective treatment for superficial BCC, BD and both individual and field treatment of AKs. Excellent cosmesis can be achieved with high patient satisfaction. Variable results have been reported for nodular BCC, with improved outcomes following pretreatment and repeated PDT cycles. The more aggressive basisquamous, morphoeic infiltrating subtypes of BCC and invasive squamous cell carcinoma (SCC) are not suitable for PDT. Prevention of “field cancerization” in organ transplant recipients on long-term immunosuppression and patients with Gorlin syndrome (naevoid basal cell carcinoma syndrome) is a promising development. The optimisation of PDT techniques with improved photosensitiser delivery to target tissues, new generation photosensitisers and novel light sources may expand the future role of PDT in NMSC management.

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“…The efficacy of photodynamic therapy (PDT) in the treatment of localized and disseminated lesions has been reported in several studies. 1,4 AKs are associated with chronic sun-exposure and ultraviolet (UV)-induced mutations in the p53 gene occur before the clinical appearance and p53 expression serve as marker of UV-B damage. 5 Mutations in other genes in the lesions have remained uninvestigated.We investigated the telomerase reverse transcriptase (TERT) promoter mutations, which create binding sites for ETS transcription factors, in AK lesions from 27 patients undergoing treatment with daylight-mediated PDT 1,4,6,7 (Fig.…”

mentioning

confidence: 99%

“…The same lesions were biopsied 3 months after the treatment. The median patient age at diagnosis was 79 years (IQR: 75-80 years) with 12 men and 15 women 1,4 (Fig. 1).…”

mentioning

confidence: 99%