title: Vemurafenib and radiosensitization.
abstract: OBJECTIVE
  The BRAF inhibitor, vemurafenib, was recently approved for the treatment of patients with BRAFV600 metastatic melanoma. Wider use of this drug and longer follow-up periods of treatment are resulting in the emergence of a growing number of reports detailing new adverse effects. Cutaneous adverse effects are preeminent with UV-A-dependent phototoxicity, hyperkeratotic folliculitis, hand-foot skin reaction, hair changes, verrucous papillomas, keratoacanthomas, and squamous cell carcinomas.
  
  
  METHODS
  We report 2 cases of dermatitis occurring on a previously irradiated skin area in patients treated with vemurafenib for a BRAFV600-mutated metastatic melanoma. The first case occurred 10 days after a low dose of radiation was delivered that usually does not induce any radiodermatitis, suggesting radiosensitization by vemurafenib. The second case occurred 30 days after radiotherapy and was diagnosed as radiation recall dermatitis.
  
  
  CONCLUSIONS
  Vemurafenib should be considered a potential cutaneous radiosensitizer and an inducer of radiation recall dermatitis. However, these adverse effects are easily managed with topical corticosteroids. Dose reduction or interruption of vemurafenib is not required. Further studies and reports will enlighten us as to whether this pharmacodynamic interaction between x-rays and vemurafenib is also seen with other BRAF or MEK inhibitors on the same mitogen-activated protein kinase pathway currently under development.
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Boussemart
authors.forename: Catherine
authors.initials: C
authors.lastname: Boivin
authors.forename: Joël
authors.initials: J
authors.lastname: Claveau
authors.forename: Yun Gan
authors.initials: YG
authors.lastname: Tao
authors.forename: Gorana
authors.initials: G
authors.lastname: Tomasic
authors.forename: Emilie
authors.initials: E
authors.lastname: Routier
authors.forename: Christine
authors.initials: C
authors.lastname: Mateus
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000532:radiotherapy; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D011836:Radiation Tolerance / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf