Erhardt Andreas, Kolligs Frank, Dollinger Matthias, Schott Eckart, Wege Hennig, Bitzer Michael, Gog Christiane, Lammert Frank, Schuchmann Markus, Walter Clemens, Blondin Dirk, Ohmann Christian, Häussinger Dieter
Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany,
Cancer Chemother Pharmacol. 2014 Nov;74(5):947-54. doi: 10.1007/s00280-014-2568-8. Epub 2014 Aug 31.
The present multicenter phase II trial investigated the combination of TACE and sorafenib for the treatment of HCC.
Eligibility criteria included histologically confirmed, unresectable HCC beyond Milan criteria, no extrahepatic spread, Child-Pugh score ≤ 8 and ECOG PS 0-2. Patients had received no prior therapy for HCC. Sorafenib was given at a dose of 400 mg/bid (interrupted only around TACE). TACE with lipiodol, 50 mg doxorubicin and polyvinyl alcohol (PVA) particles was repeated q6w as long as there was no overall disease progression. Tumor assessment by MRI was performed q6w according to EASL criteria. The primary endpoint was time to progression (TTP).
Patients (n = 43) received a mean of 2.6 ± 2.2 TACE interventions (range 0-10). Median TTP was 16.4 months (95 % CI 10.7-∞). Median overall survival (OS) was 20.1 months (95 % CI 17.6-28.2). Disease control rate according to EASL criteria was 74.4 % (7 % complete responses [CRs] + 41.8 % partial responses [PRs] + 25.6 % stable diseases [SDs]). Four patients (9 %) became amenable to either radiofrequency ablation or liver transplantation; 5 (12 %) patients died during the trial. Overall, there were 360 AEs, including 56 grade 3/4 AEs and 39 SAEs.
Combination treatment of TACE and sorafenib in the present trial was tolerable and associated with an interesting response rate, TTP and OS. Combination therapies will probably close gaps in the present mono therapy driven treatment guidelines for locally advanced HCC.
本多中心II期试验研究了经动脉化疗栓塞术（TACE）与索拉非尼联合治疗肝细胞癌（HCC）的疗效。
入选标准包括组织学确诊、超出米兰标准的不可切除HCC、无肝外转移、Child-Pugh评分≤8以及东部肿瘤协作组（ECOG）体能状态（PS）为0 - 2。患者此前未接受过HCC治疗。索拉非尼剂量为400 mg/每日两次（仅在TACE前后中断）。只要无疾病总体进展，每6周重复进行一次含碘油、50 mg阿霉素和聚乙烯醇（PVA）颗粒的TACE。根据欧洲肝脏研究学会（EASL）标准，每6周进行一次MRI肿瘤评估。主要终点为疾病进展时间（TTP）。
患者（n = 43）平均接受2.6±2.2次TACE干预（范围0 - 10）。TTP中位数为16.4个月（95%置信区间10.7 - ∞）。总生存期（OS）中位数为20.1个月（95%置信区间17.6 - 28.2）。根据EASL标准，疾病控制率为74.4%（7%完全缓解[CRs] + 41.8%部分缓解[PRs] + 25.6%疾病稳定[SDs]）。4例患者（9%）适合进行射频消融或肝移植；5例（12%）患者在试验期间死亡。总体上，共有360例不良事件（AE），包括56例3/4级AE和39例严重不良事件（SAE）。
本试验中TACE与索拉非尼联合治疗耐受性良好，且具有令人感兴趣的缓解率、TTP和OS。联合治疗可能会弥补当前局部晚期HCC单一疗法主导的治疗指南中的差距。
