title: Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer.
abstract: Sirolimus has antineoplastic effects and may reduce skin cancer rates in kidney transplant patients. This prospective, multicenter, randomized, open-label, controlled trial randomized 86 kidney transplant recipients (≥1 year posttransplant) with history of nonmelanoma skin cancer (NMSC) to continue calcineurin inhibitor (CNI) or convert to sirolimus. Patients were stratified by number of NMSC lesions (0-5, 6-20) in previous year. Primary end point was number of biopsy-confirmed new NMSC lesions per patient-year. Yearly NMSC rate was significantly lower with sirolimus (1.31 vs. 2.48 lesions/patient-year; p = 0.022). Squamous cell carcinoma occurred at a lower rate in the sirolimus versus CNI group (p = 0.038); basal cell carcinoma rate was similar in both. A lower proportion of patients receiving sirolimus developed new or recurrent NMSC (56.4% vs. 80.9%; p = 0.015) or new squamous cell carcinoma (41.0% vs. 70.2%; p = 0.006). No sirolimus patients and one CNI continuation patient experienced acute rejection. Incidence of treatment-emergent adverse events was similar between groups; however, discontinuation rates related to adverse events were significantly higher with sirolimus (46.2% vs. 0%; p < 0.001). In kidney transplant recipients with history of NMSC, conversion from CNI to sirolimus reduced rates of NMSC, without increasing acute rejection risk.
authors.affiliation: Princess Alexandra Hospital and University of Queensland, Brisbane, Australia. scottb_campbell@health.qld.gov.au
authors.forename: S B
authors.initials: SB
authors.lastname: Campbell
authors.forename: R
authors.initials: R
authors.lastname: Walker
authors.forename: S See
authors.initials: SS
authors.lastname: Tai
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: G R
authors.initials: GR
authors.lastname: Russ
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015996:Survival Rate
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus