Two-Year Randomized Controlled Prospective Trial Converting Treatment of Stable Renal Transplant Recipients With Cutaneous Invasive Squamous Cell Carcinomas to Sirolimus

Purpose In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers. Patients and Methods In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v >= 55 years) and number of previous SCCs ( one to nine v >= 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point. Results After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 ( 95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 ( 95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events. Conclusion Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years. J Clin Oncol 31:1317-1323. (C) 2013 by American Society of Clinical Oncology