Liu Bao-Jiang, Gao Song, Zhu Xu, Guo Jian-Hai, Zhang Xin, Chen Hui, Wang Xiao-Dong, Yang Ren-Jie
Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing 100142, China.
World J Gastrointest Oncol. 2020 Jun 15;12(6):663-676. doi: 10.4251/wjgo.v12.i6.663.
There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy (HAIC) after transarterial chemoembolization (TACE) for intermediate and advanced hepatocellular carcinoma (HCC). It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.
To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) after TACE for intermediate and advanced HCC.
This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACE-HAIC. All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC. Participants at our institute with intermediate and advanced HCC underwent routine TACE. Then, the catheter used for embolization was kept in place in the hepatic artery, and oxaliplatin was intra-arterially administered for 6 h, followed by 5-FU for 18 h, and folinic acid was intravenously administered for 2 h. The primary endpoints were safety, as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0, and 12-mo progression-free survival (PFS), as analyzed by the Kaplan-Meier method. As secondary endpoints, the objective response rate (ORR) was evaluated by the modified Response Evaluation Criteria for Solid Tumors, and survival time [overall survival (OS)] was analyzed by the Kaplan-Meier method.
Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study (mean age, 53.3 ± 11.7 years). Approximately 56.1% of participants had Barcelona Clinic Liver Cancer (BCLC) stage C disease, and 43.9% had BCLC stage B disease. The ORR was 42.4%. The disease control rate was 87.9%. The grade 3-4 toxicities consisted of thrombocytopenia (4.5%), neutropenia (3.0%), and elevated aspartate aminotransferase (12.2%). Hand-foot skin reaction was also observed (40.9%). The median PFS was 13.1 mo (13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants). The 6-mo, 12-mo, and 24-mo PFS rates were 75.0%, 54.7%, and 30.0%, respectively. The median OS was 21.8 mo.
Sorafenib combined with HAIC (FOLFOX) after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50% and had good patient tolerance. Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.
对于中晚期肝细胞癌（HCC），在经动脉化疗栓塞术（TACE）后将索拉非尼与肝动脉灌注化疗（HAIC）联合使用的证据很少。确定中晚期HCC患者最有可能从这种联合治疗中获益很重要。
探讨TACE后索拉非尼联合含亚叶酸、5-氟尿嘧啶（5-FU）和奥沙利铂的HAIC（FOLFOX）治疗中晚期HCC的安全性和临床疗效。
这项前瞻性II期研究纳入了接受索拉非尼联合TACE-HAIC治疗的中晚期HCC患者。所有患者在TACE-HAIC之前最初接受标准剂量400mg索拉非尼，每日两次。本研究所的中晚期HCC患者接受常规TACE。然后，将用于栓塞的导管保留在肝动脉中，动脉内给予奥沙利铂6小时，随后给予5-FU 18小时，静脉给予亚叶酸2小时。主要终点为安全性（根据不良事件通用术语标准4.0评估）和12个月无进展生存期（PFS，采用Kaplan-Meier法分析）。作为次要终点，客观缓解率（ORR）根据实体瘤改良疗效评价标准评估，生存时间[总生存期（OS）]采用Kaplan-Meier法分析。
本前瞻性研究纳入了本研究所的66例中晚期HCC患者（平均年龄53.3±11.7岁）。约56.1%的患者为巴塞罗那临床肝癌（BCLC）C期疾病，43.9%为BCLC B期疾病。ORR为42.4%。疾病控制率为87.9%。3-4级毒性包括血小板减少（4.5%）、中性粒细胞减少（3.0%）和天冬氨酸转氨酶升高（12.2%）。还观察到手足皮肤反应（40.9%）。中位PFS为13.1个月（BCLC B期患者为13.5个月，BCLC C期患者为9.4个月）。6个月、12个月和24个月的PFS率分别为75.0%、54.7%和30.0%。中位OS为21.8个月。
TACE后索拉非尼联合HAIC（FOLFOX）可能是中晚期HCC的一种可行治疗选择，因为该治疗达到了6个月PFS率超过50%的预设终点，且患者耐受性良好。需要进行前瞻性随机对照试验来证实这种联合治疗的效果。
