在早期劑量遞增研究中，索拉非尼是一種新的口服多激酶抑製劑，在0.2g bid和0.3g bid劑量水平下對治療不同類型實體瘤包括HCC均顯示出抗腫瘤活性和良好耐受性。 這項前瞻性研究旨在評估索拉非尼在晚期HCC患者中的安全性和有效性。

在這個II期研究中，招募了來自中國10個地點的患者，他們是不可切除的HCC患者或者有Child-Pugh A級肝功能並未獲得全身治療。根據1：1隨機比例，所有患者均接受口服索拉非尼0.2g bid或0.3g bid，持續數周4周。 放射學評估每8周進行一次。 主要的終點是安全和耐受性。次要終點是評估ORR，DCR和PK。

2014年6月17日至2015年5月4日，共有106例患者參加了安全性分析。 其中，52人接受了索拉非尼0.2g bid組，54人收到0.3g bid組。最常見的不良事件為10例(9.4%)患者(2例，8例)手足皮膚反應，，4例(3.8%)患者(1例vs 3例)肝功能障礙，2例(1.9%)患者(1 vs 1)白細胞減少症，導致藥物停藥或減少用量。其他導致的劑量減少的AEs是高血壓，血小板減少症，咽喉痛和咳嗽。 初始劑量持續時間分別為90和72天。TTP的完整分析包括104名患者(分別為51名和53名)，ORR和DCR的每個方案分析包括84名患者(分別為40名和44名)。 0.2g組的中位TTP為111天，0.3g組為110天(HR 0.99,95%CI [0.62,1.60])。在第16周，兩組均無完全反應，但4例(4.8%)患者(2例vs 2例)發生部分反應。 35例(41.7%)(17例，18例)患者疾病穩定。

索拉非尼0.2g bid和0.3g bid耐受性都良好。 0.3g組的重大不良事件報道較多。 兩種方案對HCC患者治療效果沒有顯著差異，因此0.2g bid似乎是治療HCC的適當的一線治療選擇。

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