关键词: 肝细胞癌（HCC）, 甲磺酸阿帕替尼, Ⅱ期临床试验

Abstract: ObjectiveTo observe and assess the efficacy and safety of different dosages of apatinib mesylate on advanced hepatocellular carcinoma（HCC）. 
MethodsIt was a prospective， randomised， openlabeled， two dosages， national multicentre， and phase Ⅱ clinical trial. From June 2010 to July 2013， a total of 121 advanced HCC patients who had not received any systemic treatment（including molecular targeted therapy and systemic chemotherapy） were enrolled from 16 centers in China. First， 104 patients were randomly allocated in a 1：1 ratio to two cohorts to receive oral apatinib at an initial dosage of 750 mg qd（n=51） or 850 mg qd（n=53）. To further explore the safety of high dosage（850 mg qd）， 17 patients were recruited to receive apatinib 850 mg qd， thus the sample of 850 mg cohort was expanded to 70 cases. The primary endpoint was median time to progression（TTP）， and the secondary endpoints included overall survival（OS）， objective response rate（ORR）， disease control rate（DCR） and adverse events（AEs）. Tumor response and AEs were evaluated according to RECIST 11 criteria and NCI CTC 40 criteria respectively. 
ResultsThe TTP of patients treated with 750 mg and 850 mg apatinib were 332 months（95％CI：2045.86 months） and 421 months（95％CI：2.14-5.86 months）， and the median OS were 9.82 months（95％CI：5.71-12.07 months） and 971 months（95％CI：6.61-12.04 months）， respectively. ORR was 2.0％ and 10.0％， and DCR were 647％ and 58.6％， respectively. No statistical differences in the above efficacy indexes were found between the two dosages（P＞0.05）. The drugrelated AEs of grade≥3 occurred in 58.8％ and 586％ patients receiving 750 mg and 850 mg apatinib（P＞005）， respectively. No unexpected AEs occurred. 
ConclusionApatinib can be used for advanced HCC. Apatinib at an initial dosage of 750 mg or 850 mg qd orally has equal efficacy and safety in advanced HCC patients with good tolerance. Hence，oral administration ofapatinib 750 mg qd is recommended for the further phase Ⅲ clinical trial.

Key words: Hepatocellular carcinoma（HCC）, Apatinib mesylate, Phase Ⅱ clinical trial