甲磺酸阿帕替尼联合经导管动脉化疗栓塞治疗肝细胞肝癌的Ⅱ期临床试验

摘要

目的:评价甲磺酸阿帕替尼(简称阿帕替尼)联合经导管动脉化疗栓塞(TACE)治疗进展期肝细胞肝癌(HCC)的安全性与疗效.方法:无手术指征的HCC患者进入此项前瞻性单中心Ⅱ期临床试验,患者口服阿帕替尼500 mg,每日1次;同时联合TACE治疗;进而评价阿帕替尼+TACE联合治疗的安全性与疗效.结果:成功完成联合治疗的患者共有30例.平均年龄:66岁;肝功能Child-Pugh A级患者:80.6%;ECOG (Eastern Cooperative Oncology Group,美国东部肿瘤协作组)体力评分0级:51.6%,1级:48.4%;肿瘤平均直径:6.5 cm.所有患者共进行60轮次联合治疗.每位患者平均2轮次治疗(1次~5次).在第一轮次治疗中常见的毒性反应为乏力(97.5%)、血压升高(75.2%)、总胆红素升高(65.3%)和皮肤反应(39.6%).虽然有患者经历有一个3~4级的药物毒性反应,但大多数的毒性反应是轻微的(1~2级毒性反应85%,3~4级毒性反应15%).在第二轮次治疗中药物毒性反应减轻.在整个临床试验中,患者因阿帕替尼药物毒性反应有21例次药物治疗中断,18例次药物减量.阿帕替尼+TACE联合治疗的疾病控制率为87.5%(根据实体肿瘤疗效评价标准),客观缓解率为10%.结论:阿帕替尼联合TACE对无手术指征的HCC患者的联合治疗是安全有效的,对阿帕替尼的药物毒性反应可以通过调整药物剂量来控制.初步的临床研究结果令人满意.%Objective:To evaluate the safety and efficacy of combined transarterial chemoembolization (TACE) and Apatinib Mesylate Tablets in patients with advanced hepatocellular carcinoma(HCC). Methods:A prospective single-center phase Ⅱ study was undertaken involving patients with unresectable HCC. The protocol involved Apa-tinib 500 mg once per day combined with TACE. The safety and efficacy were assessed. Results:Apatinib in com-bination with TACE was successfully administered in 30 patients with averaged age of 66 years,80.6% rated in Child-Pugh A,51.6% and 48.4% respectively in Eastern Cooperative Oncology Group performance status of 0 and averaged tumor size of 6.5 cm. Patients underwent 60 cycles of therapy. Median number of cycles per patients was two (range,one to five cycles). The most common toxicities during the first cycle were fatigue (97.5%),hyper-tension (75.2%),elevated total bilirubin (65.3%), and dermatologic adverse effects (39.6%). Although the patients experienced at least one grade 3 or 4 toxicity, the most toxicities were minor ones (grade 1 to 2,85%;grade 3 to 4,15%). Toxicity during the second cycle was decreased. Over the course of the study,there were 21 Apatinib dose interruptions and 18 Apatinib dose reductions. Apatinib plus TACE was associated with a disease control rate of 87.5% (Response Evaluation Criteria in Solid Tumors Group,RECIST criterion),with an objective response of 10%. Conclusions:The combination of Apatinib and TACE in patients with unresectable HCC is well tolerated and safe, with most of the toxicities related to Apatinib. Toxicity is manageable with dose adjustment of Apatinib. Preliminary efficacy data are promising.