He Min-Ke, Zou Ru-Hai, Li Qi-Jiong, Zhou Zhong-Guo, Shen Jing-Xian, Zhang Yong-Fa, Yu Zi-Shan, Xu Li, Shi Ming
Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, China.
Department of Ultrasonography, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, China.
Cardiovasc Intervent Radiol. 2018 May;41(5):734-743. doi: 10.1007/s00270-017-1874-z. Epub 2018 Jan 11.
Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results.
Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m HAI on day 1, leucovorin 400 mg/m HAI on days 1, and 5-fluorouracil 2800 mg/m on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate.
The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3-4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%).
The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial. Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).
索拉非尼被推荐用于晚期肝细胞癌（HCC）的一线治疗。然而，接受索拉非尼单药治疗的伴有主要门静脉肿瘤血栓形成的HCC患者的中位无进展生存期（PFS）不超过3个月。开展了一项前瞻性单臂II期研究，以确定在索拉非尼基础上加用奥沙利铂、5-氟尿嘧啶和亚叶酸钙的肝动脉灌注化疗是否能改善这些结果。
35例患者接受索拉非尼口服，400mg，每日2次，第1天接受奥沙利铂85mg/m²肝动脉灌注，第1天接受亚叶酸钙400mg/m²肝动脉灌注，第1天和第2天接受5-氟尿嘧啶2800mg/m²肝动脉灌注，每21天重复一次。主要终点为3个月PFS率。
3个月、6个月和12个月的PFS率分别为82.9%、51.4%和22.9%。中位PFS和总生存期分别为6.7个月和13.2个月。根据实体瘤疗效评价标准（RECIST），客观缓解率为40%，疾病控制率为77.1%。5例（14.3%）患者在研究治疗后实现了转化为完全切除，其中1例出现病理完全缓解。未发生与治疗相关的死亡。3-4级毒性包括天冬氨酸转氨酶升高（31.4%）、手足综合征（17.1%）、血小板减少（14.3%）和中性粒细胞减少（8.6%）。
联合治疗达到了预先设定的3个月无进展生存率超过65%的终点，且临床可耐受。这种方法的优点需要通过III期试验来确定。临床试验编号：http://ClinicalTrials.gov（编号NCT02981498）
