Prescription Drug Linked to Increased Skin Cancer Risk

Concerns raised over treatment that fights fungal infections in lung transplant patients.

The prescription drug voriconazole, used to treat fungal infections in lung transplant patients, has recently been found to be associated with an increased risk of skin cancer and possibly death.

This information comes from a new study by UC San Francisco researchers. The team recommends physicians consider patient-specific factors that could modify the drug’s risk and benefits when providing care.

“It is important for physicians to be aware of the impact of voriconazole on these outcomes,” said senior author 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.”

Skin cancer is the most common type of malignancy in patients who have just undergone an organ transplant. This is most likely due to immunosuppression, with recipients experiencing a greater than 65-fold increased risk of developing cutaneous squamous cell carcinoma (SCC) compared with the general population. SCCs are very aggressive and can lead to multiple lesions and the need for debilitating surgeries, increasing the risk of death in some patients.

Lung transplant patients have a particularly high risk associated with SCC due to older age at the time of transplant and more intensive immunosuppression. They also have high rates of fungal infections following transplantation, which can result in significant morbidity and mortality.

Voriconazole is used to treat fungal infections that arise after organ transplantation, particularly fungal infections caused by the Aspergillus fungi. This fungi can cause a variety of diseases that often occur in healthy people who have underlying illnesses such as tuberculosis or chronic obstructive pulmonary disease (COPD).

While voriconazole is effective in treating these ailments, SCC remains a serious side effect of taking the medication, which has no clear guidelines for prophylaxis regimens despite its widespread use.

The researchers observed patients with single-lung, double-lung, or heart-lung transplants who received their transplant between October 1991 and December 2012. Four hundred and fifty-five individuals were analyzed for voriconazole exposure and its impact on SCC, Aspergillus colonization, invasive aspergillosis, and all-cause mortality.

The results showed that the medication was associated with a 73% increased risk for SCC, with each additional 30-day exposure increasing the risk by 3%.

Moreover, the drug was found to reduce the risk of Aspergillus colonization, but had no effect on aspergillosis. It also reduced all-cause mortality among transplant recipients who developed Aspergillus colonization but had no significant impact on those without colonization.

“Among lung transplant recipients with risk factors for SCC, including those with 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 SCC,” said lead author Matthew Mansh, MD.