Use of proliferation signal inhibitors in non-melanoma skin cancer following renal transplantation

Abstract

Non-melanoma skin cancer (NMSC) affects a large proportion of renal transplant recipients, with estimates suggesting that at least half of white-skinned transplant recipients will develop NMSC following transplantation. Squamous-cell carcinoma is the most frequent NMSC following transplantation occurring at a 100-times greater risk than in the general population, while the incidence of basal cell carcinoma is increased 10-fold over the general population. The most important risk factor for the development of NMSC in renal transplant recipients is prior exposure to ultraviolet radiation, therefore, geographical location and skin type highly influence the risk of NMSC. However, both the intensity and type of immuno-suppressive therapy have been associated with an increased risk of NMSC. Given the potential anti-cancer actions of the proliferation signal inhibitors (PSIs), everolimus and sirolimus, demonstrated in both pre-clinical and clinical studies, we have analysed the effect of conversion to PSIs in 53 renal transplant recipients developing NMSC after transplantation. Remission of NMSC was observed in 37 patients and was generally well tolerated with minimal adverse events reported. Fifteen patients developed new lesions following conversion, two of these were receiving low-dose calcineurin inhibitors (CNIs) as part of their immuno-suppressive regimen suggesting that there was insufficient reduction of CNIs. PSI blood levels did not seem to affect the outcomes of conversion. These data, along with published clinical trial data suggest that conversion from CNIs to PSIs may be useful in the management of NMSC following renal transplantation.