NEJM：从钙调神经磷酸酶抑制剂换为西罗莫司降低肾移植病人患新皮肤癌

西罗莫司(sirolimus, 也译作雷帕霉素)分子结构图，图片来自维基共享资源。

根据于2012年7月26日发表在New England Journal of Medicine期刊上的一篇论文，在患有至少一种皮肤鳞状细胞癌(cutaneous squamous-cell carcinoma)的肾移植病人中，更换免疫抑制剂，即从钙调神经磷酸酶(calcineurin)抑制剂换为西罗莫司(sirolimus, 也译作雷帕霉素)与病人未患皮肤癌的存活和新皮肤癌延迟产生相关联。

来自法国里昂市爱德华-埃里奥医院集团( Edouard Herriot Hospital Group)的Sylvie Euvrard博士和同事们随机分配了120名患有至少一种皮肤鳞状细胞癌且正在接受钙调神经磷酸酶抑制剂治疗的肾移植病人，让他们继续接受钙调神经磷酸酶抑制剂治疗(56名)或者换用西罗莫司来继续治疗(64名)。

2年后，研究人员发现接受西罗莫司治疗的那组病人显著性地更加长地没有患上皮肤鳞状细胞癌地存活。而且服用西罗莫司的病人更少地患上新的皮肤鳞状细胞癌(为22%，而继续服用钙调神经磷酸酶抑制剂的病人为39%；相对危险度为0.56)，同时患上新的皮肤鳞状细胞癌所需的平均间隔期更长(15个月，而对继续服用钙调神经磷酸酶抑制剂的病人而言，则是7个月)。不过，在接受西罗莫司治疗的那组病人中，严重性不良事件更为常见，而且相比于逐渐从钙调神经磷酸酶抑制剂转换为西罗莫司的治疗过程而言，快速从钙调神经磷酸酶抑制剂转换为西罗莫司的治疗过程在病人身上产生的严重性不良事件增加了2倍。此外，23%的病人因为严重性不良事件而停止服用西罗莫司。不过，研究人员在病人身上没有观察到移植排斥发生。

Euvrard和同事们写道，“总之，在这项涉及患有至少一种皮肤鳞状细胞癌的肾移植病人的研究中，从钙调神经磷酸酶抑制剂转换为西罗莫司与更低风险患有新的皮肤癌相关联。”

本文编译自Immunosuppressant switch cuts skin cancer post-transplant

doi: 10.1056/NEJMoa1204166
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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.