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索拉非尼治疗肝移植后复发性肝细胞癌的高毒性。

High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation.

机构信息

Hepatobiliary and Transplant Surgery, University Medical Centre Hamburg -Eppendorf, Hamburg, Germany.

出版信息

Transpl Int. 2012 Nov;25(11):1158-64. doi: 10.1111/j.1432-2277.2012.01540.x. Epub 2012 Aug 6.

Abstract

Treatment options of recurrent hepatocellular carcinoma (HCC) after liver transplantation are limited and data on systemic compounds for advanced tumor stages in transplant recipients are sparse. We retrospectively analyzed the toxicity, tolerability, and efficacy of sorafenib in combination with mTOR inhibitors (mTORi), or calcineurin inhibitors (CNI) in transplant recipients with recurrent HCC. In total, 20 of 92 patients transplanted for HCC within a 10-year time period, experienced tumor recurrence. In case of ineligibility for other treatment options, patients received sorafenib (n = 13). In addition, CNI were stopped and switched to mTORi in nine patients, whereas CNI were continued in four patients. Grade 3-4 adverse events were observed in 92% of all patients necessitating sorafenib discontinuation in 77%. The most common severe adverse events were acute hepatitis, diarrhea, hand-foot - skin reaction and bone marrow suppression. In patients receiving sorafenib/mTORi one patient achieved partial response, and four achieved stable disease. In this cohort of liver transplant recipients side effects prevented full dosing of sorafenib and necessitated discontinuation of sorafenib in the majority of patients, yet antitumor efficacy seemed promising in combination with mTORi.

摘要

肝移植后复发性肝细胞癌(HCC)的治疗选择有限,且关于移植受者晚期肿瘤阶段系统化合物的数据很少。我们回顾性分析了索拉非尼联合 mTOR 抑制剂(mTORi)或钙调神经磷酸酶抑制剂(CNI)在复发性 HCC 移植受者中的毒性、耐受性和疗效。在 10 年期间,92 例 HCC 移植患者中有 20 例发生肿瘤复发。对于其他治疗方案不适用的患者,给予索拉非尼(n = 13)。此外,9 例患者停用 CNI 并转换为 mTORi,而 4 例患者继续使用 CNI。所有患者中有 92%观察到 3-4 级不良事件,需要停用索拉非尼的占 77%。最常见的严重不良事件为急性肝炎、腹泻、手足皮肤反应和骨髓抑制。在接受索拉非尼/mTORi 的患者中,1 例患者部分缓解,4 例患者病情稳定。在这组肝移植受者中,副作用使索拉非尼的剂量无法完全使用,并且大多数患者需要停用索拉非尼,但与 mTORi 联合使用似乎具有抗肿瘤疗效。

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