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

Abstract

SUMMARYLung 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.

Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation

“…Further studies on LTRs also described male sex, older age at transplantation, history of pretransplant skin cancer, Fitzpatrick skin types I and II, and dose and duration of voriconazole therapy as risk factors for posttransplant NMSC [20–22, 25].…”

Fungal Infections Complicating Lung Transplantation

“…99,100 However, long-term VCZ use has been associated with significant toxicity, including an increased risk of squamous cell carcinoma of the skin. [101][102][103][104] Therefore, VCZ should be used with caution for periods longer than a few months, especially in patients with other risk factors for skin cancer. Alternatively, POSA is effective as prophylaxis for IA in acute leukemics 105 and neutropenic patients with hematological malignancies 16 or HSCT recipients 17 and may have less toxicity with longterm use.…”

Defining Success in Lung Transplantation: From Survival to Quality of Life

“…The many complications that might occur after LT, including surgical complications, infections, episodes of allograft rejection, and extrapulmonary manifestations of transplantation may impact a patient's sense of wellbeing and ability to function independently. [23][24][25][26] In light of these complications-even if they do not result in immediate death-some in the lung transplant community are calling for success to be defined by both extended survival and improved QOL. 27,28 While the majority of the biomedical literature continues to emphasize survival time as the outcome of primary interest, clinically, considering other outcomes that are important to patients is fundamental to defining success in LT. 11,15 Success by Survival Metrics…”