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Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation
Authors:Nicholas A Kolaitis  Erin Duffy  Alice Zhang  Michelle Lo  David T Barba  Meng Chen  Teresa Soriano  Jenny Hu  Vishad Nabili  Rajeev Saggar  David M Sayah  Ariss DerHovanessian  Michael Y Shino  Joseph P Lynch III  Bernie M Kubak  Abbas Ardehali  David J Ross  John A Belperio  David Elashoff  S Samuel Weigt
Institution:1. Department of Medicine, University of California, San Francisco, CA, USA;2. Department of Medicine, University of California, Los Angeles, CA, USA;3. David Geffen School of Medicine, University of California, Los Angeles, CA, USA;4. Division of Dermatology, University of California, Los Angeles, CA, USA;5. Department of Surgery, University of California, Los Angeles, CA, USA;6. Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA;7. Department of Medicine, University of California, Los Angeles, CA, USAAuthors contributed equally.
Abstract:Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post‐transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time‐dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.
Keywords:complications (lung clinical)  fungal (infection)  quality of life (quality of life  ethics  economics)  solid tumor (malignancy and long‐term complications)
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