Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation

Transpl Int. 2017 Jan;30(1):41-48. doi: 10.1111/tri.12865. Epub 2016 Oct 24.

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).

MeSH terms

  • Aged
  • Antifungal Agents / adverse effects*
  • Carcinoma, Squamous Cell / chemically induced*
  • Female
  • Humans
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / chemically induced*
  • Time Factors
  • Voriconazole / adverse effects*

Substances

  • Antifungal Agents
  • Voriconazole