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.

A Review of Cutaneous Squamous Cell Carcinoma Epidemiology, Diagnosis, and Management

“…The increased incidence of CSCCs is tied to immunosuppressive medications, including calcineurin inhibitors (cyclosporine and tacrolimus), azathioprine, mycophenolic acid (mycophenolate mofetil and mycophenolate sodium), and prednisone (21). Recent studies have shown inhibitors of mTOR (mechanistic target of rapamycin, such as sirolimus and everolimus), to be protective against CSCC formation (22)(23)(24)(25). Some studies suggest an increase in mortality in OTRs on mTOR inhibitors; however, mortality is more likely related to higher doses of the medication (25).…”

Cancer in the Transplant Recipient

“…In the Australian study, a total of 96 kidney transplant recipients were randomized to receive maintenance CNIs or conversion to mTORIs. With a median follow-up period of 3.6 years, the overall incidence of new squamous cell skin cancer (SCC) among patients with a prior history of skin cancer was significantly lower than those on CNIs (0.88 versus 1.71 per-patient year, p ¼ 0.038) (Campbell et al 2012). A similar study, conducted in Lyons, France, randomized 120 high-risk transplanted patients with a prior history of SCCs reported a lower proportion of transplant recipients developed new SCCs in the mTORI group compared with those in the CNIs group.…”

Efficiency of late conversion from mycophenolate mofetil to everolimus in kidney graft recipients with posttransplant malignancy

“…В исследовании Campbell и соавт. через 2 года после поздней конверсии с ЦиА на эверолимус новые не меланомные кожные опухоли также выявлялись реже, чем у пациентов контрольной группы на под-держивающей ЦиА-терапии и составили 1,31 против 2,48 на пациента в год соответственно, p = 0,022 [56].…”