Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing the 302nd Hospital, 100 Xisihuan Middle Road, Beijing 100039, China.
Cell Biochem Biophys. 2012 Jun;63(2):159-69. doi: 10.1007/s12013-012-9353-2.
We assessed the safety and efficacy of sorafenib with cryotherapy (cryoRx) in advanced hepatocellular carcinoma (HCC). One hundred four HCC patients were enrolled, who met the following criteria: (i) Barcelona Clinic Liver Cancer stage C; (ii) HCC without distant metastasis; (iii) the presence of portal vein thrombosis (PVT); (iv) Child-Pugh class A or B; and (v) life expectancy of at least 12 weeks. The patients were randomly divided into sorafenib-cryoRx and sorafenib (control) groups. Primary endpoint was time to progression (TTP); secondary endpoints included overall survival (OS) and tolerability. Microvessel density (MVD) was assessed by CD34-immunostaining. After a median 10.5 (4-26) months follow-up, the data showed that median TTP was 9.5 (8.4-13.5) months in combinatorial therapy group vs. 5.3 (3.8-6.9) months in sorafenib group (P = 0.02). The median OS was 12.5 (95 % CI 10.6-16.4) months in combination therapy group vs. 8.6 (7.3-10.4) months in sorafenib group (P = 0.01). Low MVD patients in combination therapy exhibited significantly longer median TTP and OS than controls. High MVD was predictive of poor responses to sorafenib. CryoRx did not increase frequency/degree of sorafenib-related adverse events. Therefore, it was concluded that the addition of cryoRx significantly improved clinical outcomes of Sorafenib therapy in advanced HCC with acceptable tolerance and similar safety profiles as previously reported.
我们评估了索拉非尼联合冷冻治疗（cryoRx）治疗晚期肝细胞癌（HCC）的安全性和疗效。共有 104 例 HCC 患者符合以下标准：（i）巴塞罗那临床肝癌分期 C 期；（ii）无远处转移的 HCC；（iii）门静脉血栓形成（PVT）存在；（iv）Child-Pugh 分级 A 或 B；以及（v）预期寿命至少 12 周。患者随机分为索拉非尼-cryoRx 组和索拉非尼（对照）组。主要终点是无进展生存期（TTP）；次要终点包括总生存期（OS）和耐受性。微血管密度（MVD）通过 CD34 免疫组化评估。中位随访 10.5 个月（4-26 个月）后，数据显示联合治疗组中位 TTP 为 9.5 个月（8.4-13.5 个月），而索拉非尼组为 5.3 个月（3.8-6.9 个月）（P=0.02）。联合治疗组中位 OS 为 12.5 个月（95%CI 10.6-16.4 个月），而索拉非尼组为 8.6 个月（7.3-10.4 个月）（P=0.01）。联合治疗中低 MVD 患者的中位 TTP 和 OS 明显长于对照组。高 MVD 预示对索拉非尼反应不佳。CryoRx 并未增加索拉非尼相关不良事件的频率/严重程度。因此，结论是，CryoRx 的加入显著改善了晚期 HCC 患者索拉非尼治疗的临床结果，可接受的耐受性和与先前报道相似的安全性。
