在早期剂量递增研究中，索拉非尼是一种新的口服多激酶抑制剂，在0.2g bid和0.3g bid剂量水平下对治疗不同类型实体瘤包括HCC均显示出抗肿瘤活性和良好耐受性。 这项前瞻性研究旨在评估索拉非尼在晚期HCC患者中的安全性和有效性。

        在这个II期研究中，招募了来自中国10个地点的患者，他们是不可切除的HCC患者或者有Child-Pugh A级肝功能并未获得全身治疗。根据1：1随机比例，所有患者均接受口服索拉非尼0.2g bid或0.3g bid，持续数周4周。 放射学评估每8周进行一次。 主要的终点是安全和耐受性。次要终点是评估ORR，DCR和PK。

        2014年6月17日至2015年5月4日，共有106例患者参加了安全性分析。 其中，52人接受了索拉非尼0.2g bid组，54人收到0.3g bid组。最常见的不良事件为10例(9.4%)患者(2例，8例)手足皮肤反应，，4例(3.8%)患者(1例vs 3例)肝功能障碍，2例(1.9%)患者(1 vs 1)白细胞减少症，导致药物停药或减少用量。其他导致的剂量减少的AEs是高血压，血小板减少症，咽喉痛和咳嗽。 初始剂量持续时间分别为90和72天。TTP的完整分析包括104名患者(分别为51名和53名)，ORR和DCR的每个方案分析包括84名患者(分别为40名和44名)。 0.2g组的中位TTP为111天，0.3g组为110天(HR 0.99,95%CI [0.62,1.60])。在第16周，两组均无完全反应，但4例(4.8%)患者(2例vs 2例)发生部分反应。 35例(41.7%)(17例，18例)患者疾病稳定。

        索拉非尼0.2g bid和0.3g bid耐受性都良好。 0.3g组的重大不良事件报道较多。 两种方案对HCC患者治疗效果没有显著差异，因此0.2g bid似乎是治疗HCC的适当的一线治疗选择。

        查看原文：A multicenter phase II study of donafenib in patients with advanced hepatocellular carcinoma.

Abstract:

Background:In an early dose-escalation study, Donafenib, a new oral multikinase inhibitor, showed antitumor activity and favorable tolerability in treatment of different type solid tumors including HCC at both 0.2g bid and 0.3g bid dose levels. This prospective study aimed to evaluate the safety and efficacy of Donafenib in the patients with advanced HCC.In this phase 2 study, patients with unresectable HCC, who had Child-Pugh class A liver function and received no prior systemic therapy were enrolled across 10 sites in China. All patients received oral Donafenib 0.2g bid or 0.3g bid for several 4-week cycles, based on 1:1 randomization ratio. The radiology assessment was done every 8 weeks. The primary end points were safety and tolerability; secondary endpoints were time to progression assessed by an independent radiology committ, ORR , DCR, and PK.Between June 17, 2014, and May 4, 2015, total 106 patients were enrolled and included in the safety analyses. Of them, 52 received donafenib 0.2g bid and 54 received 0.3g bid. The most common adverse events that led to dose discontinuation or reductions were hand-foot skin reaction in 10 (9.4%) patients (2 vs 8), liver dysfunction in 4 (3.8%) patients (1 vs 3), and leukopenia in 2 (1.9%) patients (1 vs 1). Other reported AEs caused dose reductions were hypertension, thrombocytopenia, throat ache, and cough. The median duration maintained for the initial dose was 90 and 72 days, respectively. The full analysis set for TTP includes104 patients (51and 53, respectively) and the per-protocol analysis set for ORR and DCR includes 84 patients (40 and 44, respectively). Median TTP was 111 days in 0.2g group compared with 110 days in 0.3g group (HR 0.99, 95% CI [0.62, 1.60]). At the Week 16, there were no complete responses in both groups, but partial response was confirmed in 4 (4.8%) patients (2 vs 2); and stable disease was in 35 (41.7%) patients (17 vs 18).Donafenib 0.2g bid and 0.3g bid were well tolerated. Significant adverse events were reported more frequently in 0.3g group. Both regimens showed similar treatment responses for patients with HCC, while 0.2g bid seems to be an appropriate first line therapeutic option for the treatment of HCC. Clinical trial information:NCT02229071