title: High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients.
abstract: BACKGROUND
  Lung transplant recipients (LTR) have an increased risk of cutaneous squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole, which is associated with phototoxic side effects in some patients, may be an additional risk factor for SCC in this population.
  
  
  METHODS
  To test whether voriconazole is a risk factor for developing SCC in LTR, we evaluated cumulative exposure to voriconazole in 327 adults who underwent lung transplantation at one center between 1991 and 2010. Voriconazole exposure was assessed as a time-varying covariate. We used survival analysis methods to assess the risk of developing SCC over time.
  
  
  RESULTS
  Exposure to voriconazole was associated with a 2.6-fold increased risk for SCC. This phenomenon was dose-dependent: the risk for SCC increased by 5.6% with each 60-day exposure at a standard dose of 200 mg twice daily. At 5 years after transplant, voriconazole conferred an absolute risk increase for SCC of 28%.
  
  
  CONCLUSIONS
  These results suggest that caution should be taken when using voriconazole in LTR because this drug increases the already high risk for SCC in this population.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California at San Francisco, San Francisco, California 94115, USA. arrons@derm.ucsf.edu
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Singer
authors.forename: Andreas
authors.initials: A
authors.lastname: Boker
authors.forename: Christopher
authors.initials: C
authors.lastname: Metchnikoff
authors.forename: Maxwell
authors.initials: M
authors.lastname: Binstock
authors.forename: Rebecca
authors.initials: R
authors.lastname: Boettger
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Arron
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000453:epidemiology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole