Risk of Skin Cancers with Long-Term Itraconazole in Lung Transplant Recipients

Abstract

Purpose The objective of this study was to determine if long term itraconazole use, as antifungal prophylaxis, in lung transplant recipients is an independent risk factor for skin cancer. Methods We retrospectively reviewed patients who received a lung transplant at Mayo Clinic Rochester from 2002 to 2010. The antifungal prophylaxis protocol at our institution is triazole therapy, itraconazole or voriconazole, for a minimum of 3 years. Patients who died within 6 months of initial transplant were excluded. Characteristics to help assess independent risk for the development of cutaneous cancers and type of antifungal prophylaxis were noted. Patients who were exposed to both voriconazole and more than 6 months of itraconazole were analyzed separately. Results We identified 102 patients who underwent lung transplant at Mayo Clinic from 2002 to 2010; 11 patients died within 6 months of transplant and were excluded. Of the remaining 91 patients, 44 received only itraconazole prophylaxis, 10 received only voriconazole prophylaxis, and 37 received both itraconazole and voriconazole. No statistically significant difference between the baseline characteristics of the 3 groups was observed with the exception of race. There was a lower proportion of Caucasians in the voriconazole only group compared with the itraconazole only and combined itraconazole/voriconazole groups (p=0.02). Out of the 91 patients included in the study, 40 (44.0%) were diagnosed with skin cancer post-transplant, and 5 (12.5%) developed aggressive, metastatic cutaneous squamous cell carcinoma. Follow-up time was similar between patients who developed skin cancer (93.0 ± 45.0 months) and those who did not (62.0 ± 49.0 months, p=0.23). No significant difference was found in incidence of skin cancer or rate of metastatic squamous cell carcinoma between patients in the three groups (p=0.65) Duration of itraconazole was greater in patients who developed skin cancer [median 62.5 months (22.7, 87.5) vs 32.0 (18.0, 64.8), p=0.07] despite similar follow-up time. Absolute exposure (i.e. exposed to itraconazole or not) did not appear to correlate with the development of skin cancer post-transplant. Conclusion Prolonged itraconazole exposure when used as a prophylactic agent in lung transplant recipients appears to correlate with the development of skin cancers but further studies are warranted.