Gastrointestinal Cancer Unit, Spanish National Cancer Research Center, Fuenlabrada University Hospital, Camino del Molino 2, Fuenlabrada, Madrid, Spain.
Liver Transpl. 2012 Jan;18(1):45-52. doi: 10.1002/lt.22434.
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) = 13.4-25.1 months], and the median time to progression was 6.77 months (95% CI = 2.3-11.1 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 post-liver 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.
目前，对于肝移植后肝细胞癌（HCC）复发的最佳治疗方法尚无共识。本开放、多中心、回顾性、非对照队列研究旨在评估雷帕霉素（mTOR）抑制剂联合索拉非尼在这种情况下的安全性和初步疗效。在 31 例肝移植后 HCC 复发的患者中，改变免疫抑制治疗为 mTOR 抑制剂，并开始全身应用索拉非尼治疗。只要出现症状性肿瘤进展、死亡、肝功能失代偿或无法耐受的毒性，就维持这种联合治疗。主要治疗疗效通过总生存率和无进展生存率来确定，次要疗效通过总缓解率来确定。还分析了与使用索拉非尼和 mTOR 抑制剂相关的毒性参数。根据实体瘤反应评价标准，总缓解率为 3.8%（26 例中的 1 例），另外 13 例（50.0%）疾病持续稳定。中位总生存期为 19.3 个月[95%置信区间（CI）=13.4-25.1 个月]，中位进展时间为 6.77 个月（95%CI=2.3-11.1 个月）。仅报告了 2 例 3/4 级高血糖和 1 例 3/4 级黏膜炎，可能与 mTOR 抑制剂有关。最常见的与索拉非尼相关的严重不良事件可能是腹泻（12.9%）。总之，对于不适合根治性治疗的肝移植后 HCC 复发患者，索拉非尼联合 mTOR 抑制剂治疗尽管毒性明显，但可能是有效的。需要进一步在随机对照研究中评估这种联合治疗的疗效和毒性，以考虑其为一种有效选择。
