title: Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors.
abstract: BACKGROUND
  The treatment of metastatic melanoma has changed greatly with the development of inhibitors targeted at the mutated BRAF kinase present in up to 50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been shown to increase median survival. Unfortunately, they have also been associated with the development of verrucal keratosis (VK) and cutaneous squamous cell carcinoma (cuSCC). These lesions require surgical excision, and when a large number of these lesions need to be treated, it can significantly affect the patient's quality of life.
  
  
  OBJECTIVE
  To determine if acitretin is suitable as a chemopreventative agent against the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors.
  
  
  METHODS
  Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone more than five surgical excisions to remove lesions suggestive of cuSCC, were offered the opportunity to commence acitretin as a chemopreventative agent. Patients were evaluated every 4 weeks. Clinical and histological data were collected.
  
  
  RESULTS
  Eight patients, who had a total of 24 cuSCC removed, were included in the study. After commencement of acitretin, only five cuSCC were excised from two patients. The most significant reduction was in a patient who had developed 13 cuSCC over 10 months and only two cuSCC 3 months after commencing acitretin. No modifications in the dose of the BRAF inhibitor were made as a result of cuSCC in any of these patients.
  
  
  CONCLUSIONS
  Acitretin should be considered as a chemopreventative agent for VK and cuSCC in patients taking BRAF inhibitors, before considering dosage reductions.
authors.affiliation: Department of Dermatology(D5a), Westmead Hospital, Westmead, Sydney, NSW, 2145, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Anforth
authors.forename: T C M P
authors.initials: TC
authors.lastname: Blumetti
authors.forename: A
authors.initials: A
authors.lastname: Clements
authors.forename: R
authors.initials: R
authors.lastname: Kefford
authors.forename: G V
authors.initials: GV
authors.lastname: Long
authors.forename: P
authors.initials: P
authors.lastname: Fernandez-Peñas
mesh_terms: D017255:Acitretin / Q000627:therapeutic use*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000627:therapeutic use*; D007642:Keratosis / Q000517:prevention & control*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000601:surgery; D008875:Middle Aged; D010091:Oximes / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000601:surgery; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D016588:Anticarcinogenic Agents; D007093:Imidazoles; D007211:Indoles; D007641:Keratolytic Agents; D010091:Oximes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; D017255:Acitretin; C561627:dabrafenib