High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:31

Article

Singer, Jonathan P.¹  Boker, Andreas²  Metchnikoff, Christopher²  Binstock, Maxwell²  Boettger, Rebecca³  Golden, Jeffrey A.¹  Glidden, David V.⁴  Arron, Sarah T.¹ 

[1] Univ Calif San Francisco, Dermatol Surg & Laser Ctr, Div Pulm & Crit Care Med, San Francisco, CA 94115 USA

[2] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

关键词: voriconazole;    squamous cell carcinoma;    lung transplantation;    skin cancer;    risk factors;   

DOI  :  10.1016/j.healun.2012.02.033

来源: Elsevier

【 摘 要 】

BACKGROUND: Lung transplant recipients (LTR) have an increased risk of cutaneous squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole, which is associated with photo-toxic 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. J Heart Lung Transplant 2012;31:694-9 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

Free