Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation
Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation
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DOI：
10.1002/lt.22434
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发表时间：
2012-01-01
影响因子：
4.6
通讯作者：
Sangro, Bruno
中科院分区：
文献类型：
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作者：
Gomez-Martin, Carlos;Bustamante, Javier;Sangro, Bruno
对于肝移植后肝细胞癌（HCC）复发的最佳治疗方法，目前尚无共识。这项开放、多中心、回顾性、非对照队列研究旨在评估哺乳动物雷帕霉素靶点（mTOR）抑制剂和索拉非尼联合使用的安全性和初步疗效。在31例肝移植后HCC复发的患者中，免疫抑制治疗改为mTOR抑制剂，并开始索拉非尼全身治疗。维持该组合直至出现症状性肿瘤进展、死亡、肝失代偿或不可接受的毒性。主要疗效由总生存期和无进展生存期确定，次要疗效由总缓解率确定。还分析了与使用索拉非尼和mTOR抑制剂相关的毒性参数。根据实体瘤疗效评价标准，总有效率为3.8%（1/26），另有13例（50.0%）病情持续稳定。中位总生存期为19.3个月[95%置信区间（CI）= 13.425.1个月]，中位至进展时间为6.77个月（95% CI = 2.311.1个月）。仅报告了2例3/4级高血糖症和1例3/4级粘膜炎，可能与mTOR抑制剂相关。可能与索拉非尼相关的最常见严重不良事件是腹泻（12.9%）。总之，索拉非尼和mTOR抑制剂的联合给药可能是有效的，尽管肝移植后HCC复发患者不适合根治性治疗的显着毒性。需要在随机对照研究中进一步评价毒性和疗效，以将该组合视为有效的选择。肝移植18：4552，2012。(C)2011年AASLD。
There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation. This open, multicenter, retrospective, uncontrolled cohort study was designed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin (mTOR) inhibitor and sorafenib in this setting. In 31 patients who suffered from HCC recurrence after liver transplantation, the immunosuppressive therapy was changed to mTOR inhibitors, and systemic treatment with sorafenib was initiated. This combination was maintained until symptomatic tumor progression, death, hepatic decompensation, or unacceptable toxicity occurred. Primary treatment efficacy was determined by overall survival and progression-free survival, and secondary efficacy was determined by the overall response rate. Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed. The overall response rate according to the Response Evaluation Criteria in Solid Tumors was 3.8% (1/26), and there was sustained stabilization of the disease in 13 additional cases (50.0%). The median overall survival was 19.3 months [95% confidence interval (CI) = 13.425.1 months], and the median time to progression was 6.77 months (95% CI = 2.311.1 months). Only 2 grade 3/4 cases of hyperglycemia and 1 case of grade 3/4 mucositis were reported, and they were possibly related to mTOR inhibitors. The most common severe adverse event probably related to sorafenib was diarrhea (12.9%). In conclusion, the coadministration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with postliver transplant HCC recurrence not suitable for radical therapy. The toxicity and efficacy need to be further evaluated in randomized controlled studies for this combination to be considered a valid option. Liver Transpl 18:4552, 2012. (C) 2011 AASLD.