Produção Nacional
Revisado por pares
Conversion to Sirolimus in Renal Transplant Recipients with Skin Cancer
2006; Wolters Kluwer; Volume: 82; Issue: 12 Linguagem: Inglês
10.1097/01.tp.0000250767.67472.58
ISSN1534-6080
AutoresChiara Scaglioni Tessmer, Luiza Vieira da Silva Magalhães, Elizete Keitel, Cristiana Valar, Diego Gnatta, Ronivan Luis Dal Prá, Fabiano Roldão Silveira, Auri Ferreira dos Santos, João Carlos Goldani, Valter Duro Garcı́a, Clotilde Druck Garcia,
Tópico(s)Polyomavirus and related diseases
ResumoSkin cancers are the most common malignant occurrences in transplant recipients (1–3). It is widely recognized that immunosuppressive treatments increase the risk of skin cancer in transplant recipients (4, 5). A decrease of tumors after reduction or cessation of these drugs has been reported in aggressive disease that may lead to graft loss (6). However, some experimental studies have showed that sirolimus (SRL) slows and inhibits the growth of established experimental tumors (7) while simultaneously protecting the allograft from immunological damage (8). Clinical data has showed a lower incidence of new malignancies, after renal transplantation, in recipients under immunosuppression with a mammalian target of rapamycin inhibitor (9, 10). We report 24 renal transplant recipients with multiple skin cancers who subsequently had their immunosuppression protocol changed to SRL. The aims were to evaluate the frequency of skin cancer and renal function pre- and postintroduction of SRL. It was reviewed the patient's charts. One patient was excluded because he used SRL for less than three months and died. The creatinine clearance was calculated by the Cockcroft-Gault formula. At the time the skin cancer was diagnosed, 69.5% of the patients were using cyclosporin (CsA)+azathioprine (Aza)+prednisone (Pred), 13% Aza+Pred, 8.7% tacrolimus+ Aza+Pred, and 8.7% CsA+mofetil mycophenolate+Pred. The immunosuppression regimen consisted of an initial dose of SRL of 2 mg/day with rapid withdrawal of cyclosporine or tacrolimus and azathioprine or mofetil mycophenolate. The blood SRL level aimed was 4–10 μg/L. Prednisone was maintained at 5–10 mg/day. Statistical analysis was performed using the SPSS package. The means pre- and postconversion were analyzed by paired t test (significant P value <0.05) with a confidence interval (CI) of 95%. Of the 23 patients involved in the study, 22 were white, 15 were male, 13 received the graft from a living donor, 20 were primary transplants. The mean age was 54.3 years (SD: 12.6). The histology type of the skin cancer presented were squamous cell carcinomas (SCC; n=11), basal cell carcinomas (BCC) and SCC (n=8), melanoma (n=2), Kaposi's sarcoma (n=1) and SCC and renal cell carcinoma (n=1). The average follow-up time from transplant surgery to diagnosis of the first skin cancer was 86 months (CI: 61.5–110.8) and for the second SCC or BCC was 13.8 months (CI: 4.8–22.8). The mean follow-up time after the introduction of SRL was 22.4 months (CI: 16–28.8). Before the introduction of SRL each patient had an average of 3.2 (CI: 2.2–4.2) skin cancer episodes and after 0.7 (CI: 0.1–1.3) episodes (P<0.001). Sixteen patients had no new episodes of skin cancer. There was no acute rejection episode during the follow up. The mean creatinine clearance pre-SRL was 53 ml/min (CI: 42.4–63.6), three months post-SRL was 54.2 (CI: 43.3–65.2), six months 54.3 (CI: 42.3–63.3), one year 54.8 (CI: 40.4–69.1), and two years 55.8 (CI: 31.6–80.1). During the follow-up, two patients died (one with metastatic melanoma 11 months after conversion and another with Kaposi's sarcoma). Due to the short follow up time after conversion to SRL, it is difficult to be sure that this conversion reduces the incidence of the skin cancer. There is only one other paper published, which has evaluated the effects of the introduction of SRL in renal transplant recipients with cancer. This study showed that SRL inhibited the progression of dermal Kaposi's sarcoma while providing effective immunosuppression (11). Other clinical data reported a lower rate of skin cancer in patients treated with SRL (8, 12). An analysis in the Organ Procurement and Transplantation Network database showed a lower incidence of any new posttransplant malignancies in renal recipients with SRL/everolimus alone and SRL/everolimus plus CsA/Tac compared to CsA/Tac (0.6%, 0.6%, and 1.8%, respectively; P<0.001) even in a short-term follow-up (censored at 963 days after transplantation) (9). A multicenter trial with 430 renal transplant recipients were randomly assigned to remain on CsA+ SRL+steroids or to have CsA withdrawn three months after transplantation. A lower relative risk was demonstrated at five years, and a delay of the appearance of the first skin cancer in the group after CsA withdrawal (491 versus 1126 days; P=0.007) (10). Regarding the follow-up time, our mean time for the second skin cancer before conversion was 13.8 months and the mean follow up after conversion was 22.4 months, which could constitute a long enough exposure time for the development of new lesions. In renal transplant patients with SCC the average time for the appearance of a second tumor was 20.03 months (13). Based on the literature data and the results of this study, we plan a multicenter randomized trial of conversion to SRL in patients presenting the first episode of skin cancer. Our data suggests that in renal transplants recipients with skin cancer, conversion to SRL may reduce the incidence of new lesions, while renal function remains stable. Chiara Scaglioni Tessmer Luiza Vieira da Silva Magalhães Faculdade de Medicina Universidade Federal de Pelotas Porto Alegre, Brazil Elizete Keitel Cristiana Valar Diego Gnatta Ronivan Luis Dal Pra Fabiano Roldão Silveira Auri Ferreira dos Santos João Carlos Goldani Valter Duro Garcia Nephrology Department, Renal and Pancreas Transplant Unit Complexo Hospitalar Santa Casa Porto Alegre, Brazil Clotilde Druck Garcia Fundação Faculdade Federal de Ciências Médicas de Porto Alegre Porto Alegre, Brazil
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