Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Tsinghua University Health System, Beijing, PRC.
Anticancer Res. 2013 Jun;33(6):2797-800.
Post-transplant hepatocellular carcinoma recurrence has been reported to be between 15-18% and is higher among patients with high-risk features (bilobar tumor, macrovascular invasion, or multifocality). There are no known treatments which reduce risk of recurrence post-transplant. Sorafenib is currently approved for the treatment of advanced hepatocellular carcinoma. The objective of this phase I trial was to establish the safety and toxicity profile of sorafenib in high-risk patients with hepatocellular carcinoma who have undergone orthotopic liver transplantation.
Patients with hepatocellular carcinoma on explant with above high risk features were eligible to start the study drug between 28 and 60 days after liver transplantation. Sorafenib was administered and escalated twice daily on three cohort dose levels: i) 400 mg/day, ii) 600 mg/day and iii) 800 mg/day.
Four patients newly transplanted were enrolled and received standard post-transplant medications. Dose-limiting toxicity was reached at the first cohort dose, with three out of four patients experiencing grade 3 toxicities. One patient experienced emerging grade 3 hand foot skin reaction leading to discontinuation of the study drug. Duration of sorafenib in the four patients was 0.7 months, 1.6 months, 3.5 months and 1.6 months, respectively.
Although a small number of patients were studied, toxicity seen at 400 mg/day is consistent with toxicity reported by a small parallel study by Siegel AB.
肝移植后肝细胞癌复发率为 15-18%，且高危特征（肿瘤累及两叶、大血管侵犯或多灶性）患者的复发率更高。目前尚无已知的治疗方法可降低肝移植后复发的风险。索拉非尼目前被批准用于治疗晚期肝细胞癌。本 I 期试验的目的是确定索拉非尼在接受原位肝移植的具有肝细胞癌高危特征的患者中的安全性和毒性特征。
肝移植后肿瘤具有上述高危特征的肝细胞癌患者在肝移植后 28-60 天内开始使用研究药物。索拉非尼每天两次给药，并在三个剂量组中进行递增：i）400mg/天，ii）600mg/天，iii）800mg/天。
新移植的 4 名患者入组并接受了标准的移植后药物治疗。在第一个剂量组中达到了剂量限制毒性，4 名患者中有 3 名出现 3 级毒性。1 名患者出现新发的 3 级手足皮肤反应，导致研究药物停药。4 名患者接受索拉非尼治疗的时间分别为 0.7 个月、1.6 个月、3.5 个月和 1.6 个月。
尽管研究患者人数较少，但 400mg/天的毒性与 Siegel AB 的一项小型平行研究报告的毒性一致。
