Voriconazole may be associated with squamous cell carcinoma risk in lung transplants

Lung transplant recipients who were treated with voriconazole to prevent aspergillosis were significantly more likely than those who did not receive voriconazole to develop squamous cell carcinoma, according to a study.

Monica E. D’Arcy, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and colleagues raised the question of the association between voriconazole and keratinocyte carcinoma risk in individuals who had received a lung transplant. Voriconazole is used to treat aspergillosis, which can frequently be fatal in the transplant setting. “Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC),” D’Arcy and colleagues wrote.

Data for the population-based cohort study were culled from the national Scientific Registry of Transplant Recipients and included 9,599 non-Hispanic white individuals who underwent lung transplant procedures from Jan. 1, 2007, to Dec. 31, 2016.

In addition to voriconazole, the researchers investigated parameters associated with exposure to antifungal medications itraconazole and posaconazole.

First SCC or basal cell carcinoma (BCC) reported to the transplant registry served as the primary outcome measure.

The median age at transplant was 59 years among the 9,793 procedures performed in the 9,599 participants. The cohort was 59.5% male, with 58.4% ever smokers.

The median follow-up duration was 3 years after the procedure. In that period, the researchers reported the occurrence of 1,031 SCCs (incidence, 322 per 10,000 person-years) and 347 BCCs (incidence, 101 per 10,000 person-years).

Primary endpoint results showed that transplant recipients with 1 to 3 months of voriconazole use had a significantly increased likelihood of developing SCC compared with recipients with no history of voriconazole use (adjusted HR = 1.09; 95% CI, 0.90-1.31). Also compared with no voriconazole use, recipients who used voriconazole for 4 to 7 months (adjusted HR = 1.42; 95% CI, 1.16-1.73), 8 to 15 months (adjusted HR = 2.04; 95% CI, 1.67-2.50) and more than 15 months (adjusted HR = 3.05; 95% CI, 2.37-3.91) carried an elevated SCC risk.

Ever exposure to itraconazole resulted in an increased risk for SCC (adjusted HR = 1.20; 95% CI, 1.00-1.45).

Outcomes pertaining to BCC showed no association between risk and voriconazole use. However, both itraconazole use (adjusted HR = 1.74; 95% CI, 1.27-2.37) and posaconazole use (adjusted HR = 1.55; 95% CI, 1.00-2.41) demonstrated associations with BCC risk.

“These findings suggest that physicians caring for lung transplant recipients at high risk for aggressive keratinocyte carcinomas should limit voriconazole exposure when possible and encourage skin protection behaviors and more frequent cancer screenings,” D’Arcy and colleagues wrote.