Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study |
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| Authors: | B Hamandi C Fegbeutel F P Silveira E A Verschuuren M Younus J Mo J Yan P Ussetti P V Chin‐Hong A Solé C L Holmes‐Liew E M Billaud P A Grossi O Manuel D J Levine R G Barbers D Hadjiliadis J Aram L G Singer S Husain |
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| Institution: | 1. Department of Pharmacy, University Health Network, Toronto, ON, Canada;2. Department of Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany;3. Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA;4. Department of Pulmonary Diseases, University Hospital Groningen, Groningen, the Netherlands;5. Pfizer Inc., New York, NY, USA;6. Respiratory Department, Hospital Puerta de Hierro, Madrid, Spain;7. Department of Medicine, University of California, San Francisco, San Francisco, CA, USA;8. Respiratory Department, University and Polytechnic Hospital La Fe, Universidad de Valencia, Valencia, Spain;9. Lung Research, Hanson Institute, and Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia;10. Service de Pharmacologie, AP‐HP, H?pital Européen G Pompidou, Paris, France;11. Infectious Diseases Department, University of Insubria, Varese, Italy;12. Infectious Diseases Service and Transplantation Center, University Hospital of Lausanne, Lausanne, Switzerland;13. Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center San Antonio, TX, USA;14. Division of Pulmonary and Critical Care, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;15. Department of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA, USA;16. Toronto Lung Transplant Program, University Health Network, Toronto, ON, Canada;17. Multi‐Organ Transplant Program, University Health Network, Toronto, ON, Canada |
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| Abstract: | This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005‐2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time‐dependent variables, on the risk of developing biopsy‐confirmed SCC. Nine hundred lung transplant recipients were included. Median follow‐up time from transplantation to end of follow‐up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31‐4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07‐11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC . EU PAS registration number: EUPAS5269. |
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| Keywords: | antibiotic: antifungal clinical research/practice complication: malignant health services and outcomes research infection and infectious agents ‐ fungal infectious disease lung disease lung transplantation/pulmonology patient safety |
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