西罗莫司与肾移植术后皮肤癌二级预防。

Sirolimus and secondary skin-cancer prevention in kidney transplantation.

机构信息

Department of Dermatology, Hospices Civils de Lyon, Edouard Herriot Hospital Group, Lyon, France.

出版信息

N Engl J Med. 2012 Jul 26;367(4):329-39. doi: 10.1056/NEJMoa1204166.

DOI:10.1056/NEJMoa1204166

PMID:22830463

Abstract

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. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).

摘要

背景

患有皮肤鳞状细胞癌的移植受者发生多种后续皮肤癌的风险很高。西罗莫司是否可用于预防继发性皮肤癌尚未得到评估。

方法

在这项多中心试验中，我们将接受钙调磷酸酶抑制剂且至少患有一处皮肤鳞状细胞癌的移植受者随机分配，分别接受西罗莫司替代钙调磷酸酶抑制剂（64 例）或维持初始治疗（56 例）。主要终点是 2 年内无鳞状细胞癌生存。次要终点包括新发鳞状细胞癌的发病时间、其他皮肤肿瘤的发生、移植物功能和西罗莫司的相关问题。

结果

与钙调磷酸酶抑制剂组相比，西罗莫司组无皮肤鳞状细胞癌的生存时间明显更长。总的来说，西罗莫司组有 14 例（22%）患者（停用西罗莫司后有 6 例）和钙调磷酸酶抑制剂组有 22 例（39%）患者（中位发病时间，15 个月比 7 个月；P=0.02）新发鳞状细胞癌，西罗莫司组的相对风险为 0.56（95%置信区间，0.32 至 0.98）。西罗莫司组有 60 例严重不良事件，而钙调磷酸酶抑制剂组有 14 例（平均 0.938 比 0.250）。采用快速方案转换为西罗莫司的患者严重不良事件发生率是采用渐进方案的两倍。西罗莫司组有 23%的患者因不良事件而停药。两组研究的移植物功能均保持稳定。