Sirolimus Protects Organ Transplant Recipients from Cutaneous Squamous Cell Carcinomas

Organ transplant recipients require long-term immunosuppressive therapy to prevent rejection, which greatly increases risk for squamous cell carcinomas (SCCs) of the skin. Sirolimus is a newer anti-rejection medication that, unlike other transplant drugs, blocks the mTOR signal transduction pathway; this action not only prevents transplant rejection but, in experimental systems, also prevents SCC development.

Investigators conducted a randomized, multicenter trial to determine if sirolimus would reduce the number of additional SCCs in 120 renal transplant recipients who had already had a cutaneous SCC. Approximately half of patients were switched from the calcineurin inhibitor (cyclosporine, tacrolimus) that they were already taking to sirolimus; the other half continued on the calcineurin inhibitor at the same dose. During 2 years of follow-up, the mean time to the next SCC was significantly longer in sirolimus recipients than in calcineurin inhibitor recipients (15 months vs. 7 months); the difference was significant in patients with one previous SCC, but not in those with more than one. Adverse events causing drug discontinuation occurred in 23% of patients; serious adverse events were more common among sirolimus recipients than calcineurin inhibitor recipients. Neither group experienced any rejections.