Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis.

BACKGROUND: Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. OBJECTIVES: To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. METHODS: The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. RESULTS: Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. CONCLUSIONS: The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. OBJECTIVES: To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo. METHODS: The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3:3:1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3months after treatment, PDT was repeated. RESULTS: PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P<0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P<0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment-related adverse events were observed for the narrow- and broad-spectrum light sources. CONCLUSIONS: BF-200 ALA is a very effective, well-tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.

Two cases of squamous cell carcinoma treated with topical imiquimod 5%.

We report the first two cases of squamous cell carcinoma successfully treated with imiquimod 5% cream as a monotherapy. Imiquimod is a new immunomodulating drug that is registered for genital HPV infection but has also shown good efficacy in several cutaneous malignancies.

[Basal cell carcinoma of the foot. Is the pedoscope a risk factor?]. / Basalzellkarzinom am FussIst das Pedoskop ein Risikofaktor?

Basal cell carcinomas of the foot are absolutely rare. We describe the case of a 72-year-old female patient who developed a multicentric superficial BCC present on the lateral edge of the right foot. The patient remembers the regular control of the fit of footwear by an X-ray apparatus, the so-called shoe fluoroscope (=Pedoskop in Germany). Probably this may be a hardly estimated risk factor in the genesis of BCC of the foot.

[Occult dermal primary melanoma in congenital nevus-cell nevus]. / Okkultes dermales Primärmelanom in kongenitalem Nävuszellnävus.

Malignant melanomas normally arise at the dermoepidermal junction. Development of these tumours in deeper layers of the dermis without having contact with the junction is rare. A small congenital melanocytic nevus localized in the region of the waist band was excised because of mechanical irritation; it had not shown any changes over years. A thorough examination of the whole body did not give any clue to a malignant melanoma. Histologically a compound nevus with the typical architecture of a congenital melanocytic nevus was found. In the deeper dermis there was an isolated nodule of extremely atypical melanocytes with minimal pigmentation of melanin. S100 antigen could be demonstrated throughout the whole tumour whereas HMB45 was only found at the dermoepidermal junction. There was no marking of the tumour cells with a pancytokeratin antibody. A histological relationship between the new tumour and a mixed tumour of the left testicle, which had been excised 3 years ago, could be excluded. We did not find any metastases neither by image-aided methods nor by sentinel lymph node biopsy.

[Follicular dyskeratosis: successful treatment with local retinoid]. / Dyskeratosis follicularis--erfolgreiche Therapie mit lokalem Retinoid.

Therapy of Darier disease is rarely satisfactory. Oral retinoids can improve the skin lesions. Because of previous positive results with topical retinoids, which were often not practical because of marked skin irritation, two patients were treated with the new, topical acetylene-retinoid tazarotene in a 0.01% gel preparation. In both patients skin cleared within 2 to 4 weeks. After stopping the medication patients did not develop any new skin lesions for 12 months. In a third patient, healing with tazarotene gel 0.025% was faster than with a topical preparation containing 10% urea. Tazarotene is an important addition to the therapeutic possibilities in Darier disease.

[Symmetrical cyanosis circumscripta e lipomate]. / Symmetrische Cyanosis circumscripta e lipomate.

We report the case of a 78-year-old woman with a symmetrical type of cyanosis circumscripta e lipomate above both knees. Clinical symptoms, pathogenesis and possible treatments are presented.