The clinical impact of hedgehog pathway inhibitors and statin therapy in the treatment of locally advanced basal cell carcinoma: A case report

2021 ◽  
Author(s):  
Luciana Trane ◽  
Flavia Silvestri ◽  
Federico Venturi ◽  
Biancamaria Zuccaro ◽  
Federica Scarfì ◽  
...  
2021 ◽  
Author(s):  
Vincenzo De Giorgi ◽  
Luciana Trane ◽  
Giulia Pieretti ◽  
Nicola Santoro ◽  
Flavia Silvestri ◽  
...  

Background: The management of difficult-to-treat periocular basal cell carcinoma becomes very challenging in cases of delayed diagnosis, leading to the development of locally advanced basal cell carcinoma.Objective: The aim of this study was to evaluate the outcomes of Hedgehog pathway inhibitors (vismodegib and sonidegib)  treatment in patients affected by periocular locally advanced basal cell carcinoma. We focused on the common adverse events  and their correlation with the administration schedule  in order to determine a management protocol specific for the periocular area.Methods:  This observational prospective study included a single-center case series with patients who were histologically confirmed to have periocular or orbital locally advanced basal cell carcinoma,  treated with Hedgehog pathway inhibitors.Results: All patients benefitted in terms of regression or stabilization of the neoplasm. In the first months of treatment, the HPIs were well tolerated, and the first important side effects appeared after about 5 months of continuous use of the drug.Conclusion: These data could lead to a new type of therapeutic scheme where neoadjuvant therapy could be followed by pulse therapy as an adjuvant to surgery.


Chemotherapy ◽  
2020 ◽  
Vol 65 (1-2) ◽  
pp. 2-10 ◽  
Author(s):  
Elena Campione ◽  
Monia Di Prete ◽  
Flavia Lozzi ◽  
Caterina Lanna ◽  
Giulia Spallone ◽  
...  

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.


2021 ◽  
Vol 68 (2) ◽  
pp. 94-98
Author(s):  
Srdjan Milanovic ◽  
Suzana Stojanovic-Rundic ◽  
Nikola Milosevic ◽  
Branko Dozic ◽  
Marko Dozic

Skin cancers are the most common malignant tumors in general. The most significant risk factor is exposure to UV radiation. They mainly occur in the head and neck region, and the majority of about 80% are basal cell carcinomas. Surgery is standard treatment of uncomplicated basal cell carcinomas, but a multidisciplinary approach is necessary in advanced cases. The case report refers to a patient with locally advanced recurrent basal cell carcinoma with primary tumor localization in the right auricle and parotid region in 2012 when primary surgery was performed. Due to the local recurrence, amputation of the right auricle and trepanation of the mastoid process was done in November 2018, and after that, radiation therapy of a recurrent tumor in the area of the trepanation cavity was applied. In the course of follow-up so far, there is good local control, without signs of toxicity. The case report points to the importance of a multidisciplinary approach and the role of radiotherapy in the treatment and control of advanced basal cell carcinoma of this region.


2021 ◽  
pp. 1-2
Author(s):  
Jan Maschke

Die Publikation von Dummer et al. beschreibt die Daten zur Effektivität und Sicherheit des Hedgehog pathway Inhibitors (HPI) Sonidegib in der abschließenden 42-Monatsanalyse der BOLT (basal cell carcinoma outcomes with LDE225 (sonidegib) treatment) Studie. Ursprünglich wurden 230 erwachsene, nicht systemisch mit HPI vorbehandelte Patienten mit Basalzellkarzinomen (BCC), die nicht für eine kurative chirurgische Behandlung oder eine Bestrahlung in Frage kamen, in 58 Zentren aus 12 Ländern zwischen dem 20. Juli 2011 und dem 10. Januar 2013 eingeschlossen. Die primäre Datenanalyse fand 6 Monate nach der Randomisierung des letzten Patienten statt. Diese wurden im Verhältnis 1:2 für die Behandlung mit 200mg (n = 79) oder 800mg (n = 151) Sonidegib pro Tag per os randomisiert. Auf eine zweckmäßige Vergleichstherapie wurde verzichtet, weil bei diesen Patienten mit lokal fortgeschrittenem Basalzellkarzinom (locally advanced Basal Cell Carcinoma, laBCC) oder metastasiertem Basalzellkarzinom (mBCC) keine Spontanremission zu erwarten sei und bei Beginn der Studie kein geeigneter Komparator zur Verfügung stand (die Zulassung von Vismodegib als HPI beim BCC erfolgte 2013). Die Behandlung erfolgte bis zum Fortschreiten der Erkrankung, dem Auftreten von nicht tolerabler Toxizität, bis zum Studienende, dem Rückzug des Einverständnisses oder dem Versterben der Patienten. In Bezug auf die Effektivität wurde das objektivierbare Tumoransprechen (Objective Response Rate, ORR) bei laBCC anhand von modifizierten RECIST (mRECIST) Kriterien durch ein zentrales Gutachterboard bewertet oder mithilfe der RECIST Kriterien bei mBCC. Die Sicherheitsanalyse wurde über die kontinuierliche Dokumentation und Überwachung der unerwünschten Ereignisse (adverse events, AE) vorgenommen.


Author(s):  
Diya M Sabu ◽  
Jeska Kroes ◽  
Charles Gilham ◽  
Ann Fleming ◽  
Fergal C Kelleher

2009 ◽  
Vol 361 (12) ◽  
pp. 1164-1172 ◽  
Author(s):  
Daniel D. Von Hoff ◽  
Patricia M. LoRusso ◽  
Charles M. Rudin ◽  
Josina C. Reddy ◽  
Robert L. Yauch ◽  
...  

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