索拉非尼治疗肝细胞癌肝移植术后复发的疗效

Efficacy of sorafenib in the treatment of recurrent hepatocellular carcinoma after liver transplantation

目的探讨索拉非尼治疗肝细胞癌肝移植术后肿瘤复发或转移晚期患者的疗效及不良反应。方法回顾性分析我院2008年1月至2020年10月收治的40例肝细胞癌肝移植术后发生复发或转移患者的临床资料,观察患者口服索拉非尼(400 mg,2次/日)治疗的近期疗效、远期生存及安全性。近期疗效采用RECIST1.1标准进行评估;生存分析采用Kaplan-Meier法并行Log-rank检验;不良反应按照NCI-CTC 3.0版标准进行评估。结果40例患者均可进行疗效评价,完全缓解(CR)0例,部分缓解(PR)3例,疾病稳定(SD)9例,客观有效率(ORR)为7.5%,疾病控制率(DCR)为30.0%。索拉非尼治疗的中位持续时间为7.1个月(范围:1~36个月)。至随访截止日期,40例患者中有25例死亡。全组患者的中位PFS为7.1个月(95%CI:4.086~10.114),中位OS为21.1个月(95%CI:10.584~31.616);相较于早期复发的肝移植患者,索拉非尼明显延长肝移植10个月后复发患者的中位OS(29.6个月vs.14.7个月,P=0.032)。不良反应主要为CTCAE 1~2级,包括腹泻、手足皮肤反应、高血压、皮疹、肝功能异常、蛋白尿等。结论索拉非尼对肝细胞癌肝移植术后复发或转移的晚期患者有一定的疗效,特别是移植10个月以后复发的患者疗效更为显著,但这一结论仍需要前瞻性研究证实。

Objective To investigate the efficacy and safety of sorafenib in the treatment of recurrence or metastasis after liver transplantation for hepatocellular carcinoma(HCC).Methods The clinical data of 40 advanced patients with recurrence or metastasis of hepatocellular carcinoma after liver transplantation from Jan 2008 to Oct 2020 in our hospital were analyzed retrospectively.The short-term efficacy,long-term survival and safety of sorafenib 400 mg orally twice daily were observed.The recent efficacy was evaluated by RECIST1.1.The survival was conducted by Kaplan Meier method and the Log-rank test was used.Adverse reactions were evaluated according to NCI-CTC version 3.0.Results Among the 40 patients,there were 0 cases of complete remission(CR),3 cases of partial remission(PR),9 cases of stable disease(SD).The objective effective rate(ORR)was 7.5%,and the disease control rate(DCR)was 30.0%.The median duration of sorafenib treatment was 7.1 months(range:1-36 months).By the end of follow-up,25 of 40 patients died.The median progression-free survival(PFS)was 7.1 months(95%CI:4.086-10.114),and the median overall survival(OS)was 21.1 months(95%CI:10.584-31.616).Compared with the patients with early recurrence,sorafenib significantly increased median OS with patients recurring beyond 10 months after liver transplantation(29.6 months vs.14.7 months,P=0.032).Adverse events were mainly CTCAE grade 1 to 2,including diarrhea,hand and foot skin reaction,hypertension,rash,abnormal liver function,proteinuria,etc.Conclusion Sorafenib is effective in advanced patients with recurrence or metastasis of HCC after liver transplantation,especially in patients with recurrence beyond 10 months after transplantation.This conclusion still needs to be confirmed by prospective clinical studies.