西羅莫司(sirolimus, 也譯作雷帕霉素)分子結(jié)構(gòu)圖,，圖片來自維基共享資源。
根據(jù)于2012年7月26日發(fā)表在New England Journal of Medicine期刊上的一篇論文,，在患有至少一種皮膚鱗狀細胞癌(cutaneous squamous-cell carcinoma)的腎移植病人中,，更換免疫抑制劑，即從鈣調(diào)神經(jīng)磷酸酶(calcineurin)抑制劑換為西羅莫司(sirolimus, 也譯作雷帕霉素)與病人未患皮膚癌地存活和新皮膚癌延遲產(chǎn)生相關(guān)聯(lián),。
來自法國里昂市愛德華-埃里奧醫(yī)院集團( Edouard Herriot Hospital Group)的Sylvie Euvrard博士和同事們隨機分配了120名患有至少一種皮膚鱗狀細胞癌且正在接受鈣調(diào)神經(jīng)磷酸酶抑制劑治療的腎移植病人,，讓他們繼續(xù)接受鈣調(diào)神經(jīng)磷酸酶抑制劑治療(56名)或者換用西羅莫司來繼續(xù)治療(64名)。
2年后,，研究人員發(fā)現(xiàn)接受西羅莫司治療的那組病人顯著性地更加長地沒有患上皮膚鱗狀細胞癌地存活,。而且服用西羅莫司的病人更少地患上新的皮膚鱗狀細胞癌(為22%，而繼續(xù)服用鈣調(diào)神經(jīng)磷酸酶抑制劑的病人為39%,；相對危險度為0.56),，同時患上新的皮膚鱗狀細胞癌所需的平均間隔期更長(15個月，而對繼續(xù)服用鈣調(diào)神經(jīng)磷酸酶抑制劑的病人而言,，則是7個月),。不過，在接受西羅莫司治療的那組病人中,，嚴重性不良事件更為常見,，而且相比于逐漸從鈣調(diào)神經(jīng)磷酸酶抑制劑轉(zhuǎn)換為西羅莫司的治療過程而言，快速從鈣調(diào)神經(jīng)磷酸酶抑制劑轉(zhuǎn)換為西羅莫司的治療過程在病人身上產(chǎn)生的嚴重性不良事件增加了2倍,。此外,，23%的病人因為嚴重性不良事件而停止服用西羅莫司。不過,，研究人員在病人身上沒有觀察到移植排斥發(fā)生,。
Euvrard和同事們寫道,，“總之，在這項涉及患有至少一種皮膚鱗狀細胞癌的腎移植病人的研究中,，從鈣調(diào)神經(jīng)磷酸酶抑制劑轉(zhuǎn)換為西羅莫司與更低風險患有新的皮膚癌相關(guān)聯(lián),。”(生物谷：Bioon.com)
本文編譯自Immunosuppressant switch cuts skin cancer post-transplant
doi: 10.1056/NEJMoa1204166
PMC:
PMID:
Sirolimus and Secondary Skin-Cancer Prevention in Kidney Transplantation
Sylvie Euvrard, M.D., Emmanuel Morelon, M.D., Ph.D., Lionel Rostaing, M.D., Ph.D., Eric Goffin, M.D., Anabelle Brocard, M.D., Isabelle Tromme, M.D., Nilufer Broeders, M.D., Veronique del Marmol, M.D., Ph.D., Valérie Chatelet, M.D., Anne Dompmartin, M.D., Ph.D., Michèle Kessler, M.D., Andreas L. Serra, M.D., Günther F.L. Hofbauer, M.D., Claire Pouteil-Noble, M.D., Ph.D., Josep M. Campistol, M.D., Ph.D., Jean Kanitakis, M.D., Adeline S. Roux, M.Sc., Evelyne Decullier, Ph.D., and Jacques Dantal, M.D., Ph.D. for the TUMORAPA Study Group
BACKGROUND Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. METHODS In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus. RESULTS Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups. CONCLUSIONS Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas.
