Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Latest evidence regarding the effects of photosensitive drugs on the skin: pathogenetic mechanisms and clinical manifestations

Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy

High-Risk Recurrence Basal Cell Carcinoma: Focus on Hedgehog Pathway Inhibitors and Review of the Literature

open12noFunding Sources: This research was made possible by an unrestricted grant from Sun Pharmaceuticals.Basal cell carcinoma is the most common skin tumour, with the majority of the cases occurring on the head and neck district, where cosmetic and functional results are crucial. It can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for most lesions, but aggressive, recurrent, or unresectable tumours can be challenging to manage. Advanced basal cell carcinoma includes high recurrence risk subtypes, in which standard therapies demonstrate lack of efficacy. This led to a need for investigating more deeply the pathogenesis of the disease and to the discovery of the implication of the hedgehog pathway. The development of systemic inhibitors of this pathway provides new treatment options for patients with advanced disease, resulting in survival improvement. Food and Drug Administration, before, and European Medicines Agency later approved 2 Hedgehog pathway inhibitors for the treatment of advanced basal cell carcinomas, vismodegib and sonidegib. Here, we present a review of the current English language literature trying to analyze differences in the 2 drugs as a head-to-head comparison between them has not already been documented in a randomized controlled clinical trial. Although vismodegib and sonidegib showed similar efficacy and safety profiles, in an indirect comparison scenario, sonidegib has shown slightly better outcomes in locally advanced basal cell carcinoma than vismodegib. They present different molecular structures, as they bind different residues on their targets and develop resistance for different mutations. In a future scenario, clinical trials comparing the 2 drugs are needed, as well as expanding data on discontinuation of therapy and/or consequential administration of them, with the aim to improve our clinical practise.openElena Campione, Monia Di Prete, Flavia Lozzi, Caterina Lanna, Giulia Spallone, Mauro Mazzeo, Terenzio Cosio, Cristina Rapanotti, Emi Dika, Roberta Gaziano, Augusto Orlandi, Luca BianchiElena Campione, Monia Di Prete, Flavia Lozzi, Caterina Lanna, Giulia Spallone, Mauro Mazzeo, Terenzio Cosio, Cristina Rapanotti, Emi Dika, Roberta Gaziano, Augusto Orlandi, Luca Bianch

Patidegib in Dermatology: A Current Review

Background: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. Methods: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. Results: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naive patients with stage II and III basal cell carcinomas, while stage IV disease and not-naive patients did not show any benefit. Conclusion: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies

Early clinical response to 5-fluorouracil 0.5% and salicylic acid 10% topical solution in the treatment of actinic keratoses of the head: an observational study

Background Actinic keratosis is one of the most common dermatological disorders. A new topical solution, constituted by 0.5% 5-fluorouracil and 10% salicylic acid (Actikerall, Almirall) has been introduced in the treatment pipeline of hyperkeratotic actinic keratoses of the head and neck. Patients and methods We analyzed in an observational prospective clinical study the short-term treatment effectiveness of 5-fluorouracil and salicylic acid on face and scalp actinic keratoses of grade 1 and 2 of 40 patients. Efficacy assessment was performed by clinical dermatological examination, collecting color photographs, calculating AKASI score, and by means of dermoscopy for each target lesion at every visit. Results AKASI score decreased from an initial score of 3.3 to a final score of 0.9. At week 4, we were able to record a complete clearance of 50% of the treated lesions and a partial clearance of 28%. At the end of 12 weeks, 84% of the total lesions showed complete clearance, while 8% had partial clearance. Conclusions 5-fluorouracil and salicylic acid topical solution is effective in the treatment of mild to moderate actinic keratoses. In the future, further studies are needed to evaluate the chance of adjusting drug dosage according to patients' and actinic keratoses features