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Antifungal Agent Increases Risk of Cutaneous Squamous Cell Carcinoma in Some Lung Transplant Recipients

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Key Points

  • Voriconazole exposure resulted in a 73% greater risk for cutaneous squamous cell carcinoma.
  • Each additional 30-day exposure increased risk by 3%.
  • Researchers recommend limited exposure to high doses of voriconazole, or alternative pharmacologic options, for prevention and treatment of fungal infection in transplant recipients at high risk for skin cancer.

Voriconazole, commonly used to prevent and treat fungal infections in lung transplant recipients, significantly increases the risk for cutaneous squamous cell carcinoma in this population, according to a new study by University of California San Francisco researchers. The team recommends physicians consider patient-specific factors that could modify the drug's risks and benefits when providing care. Their study was published by Mansh et al in the American Journal of Transplantation.

“It is important for physicians to be aware of the impact of voriconazole on these outcomes,” said Sarah Arron, MD, PhD, Associate Professor of Dermatology and Director of the UCSF High Risk Skin Cancer Clinic. “We recommend that all providers counsel lung transplant recipients on skin cancer risk and photoprotection, in addition to scheduling routine skin cancer screening with a trained dermatologist after transplantation. Lung transplant programs should also consider patient-specific risk factors when deciding on the type, dose, and duration of antifungal prophylaxis regimens.”

Increased Susceptibility

Skin cancer is the most common malignancy to occur in recipients of solid organ transplants, primarily due to immunosuppression, with recipients experiencing a greater than 65-fold increased risk of developing cutaneous squamous cell carcinoma compared to the general population. Lung transplant recipients are particularly susceptible to cutaneous squamous cell carcinoma due to older age at transplant and more intensive immunosuppression. They also have high rates of fungal infections after transplant, which can result in significant morbidity and mortality.

First approved in 2002, voriconazole is used to prevent and treat invasive fungal infections like those caused by the Aspergillus fungi, especially in patients with compromised immune systems such as following a lung or other organ transplant. The Aspergillus fungi can cause aspergillosis, a variety of diseases often occurring in people with healthy immune systems but having an underlying illness, such as tuberculosis or chronic obstructive pulmonary disease.

Cutaneous squamous cell carcinoma is a serious side effect of voriconazole in lung transplant recipients.

Study Findings

In their study, Dr. Mansh, Dr. Arron, and their colleagues evaluated single-lung, double-lung, or heart-lung transplant recipients receiving a transplant at UCSF between October 1991 and December 2012. These 455 individuals were analyzed for voriconazole exposure and its impact on cutaneous squamous cell carcinoma, Aspergillus colonization, invasive aspergillosis, and all-cause mortality.

The researchers found that voriconazole exposure resulted in a 73% greater risk for cutaneous squamous cell carcinoma, with each additional 30-day exposure increasing the risk by 3%.

Further, the drug significantly reduced the risk of Aspergillus colonization, especially in the first year after transplant, but not aspergillosis. It was also associated with reduced all-cause mortality among those transplant recipients who developed Aspergillus colonization, but it had no significant impact on all-cause mortality in those transplant recipients without Aspergillus colonization.

“Among lung transplant recipients with risk factors for cutaneous squamous cell carcinoma [including older age, male sex, and white race], or those in whom prolonged voriconazole administration may not have clear benefit, transplant physicians should consider limiting exposure to high doses of voriconazole or using alternative pharmacologic options that do not pose an increased risk for cutaneous squamous cell carcinoma,” said Matthew Mansh, MD.

Dr. Arron is the corresponding author for the American Journal of Transplantation article.

This study was supported by a Stanford University Medical Scholars Research Grant; the National Institutes of Health National Center for Advancing Translational Sciences through the UCSF Clinical and Translational Science Institute; the NIH National Heart, Lung, and Blood Institute; and the UCSF Nina Ireland Lung Disease Program.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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