Yang Yongping, Lu Yinying, Wang Chunping, Bai Wenlin, Qu Jianhui, Chen Yan, Chang Xiujuan, An Linjing, Zhou Lin, Zeng Zhen, Lou Min, Lv Jiyun
Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing 302nd Hospital;
Exp Ther Med. 2012 Feb;3(2):171-180. doi: 10.3892/etm.2011.398. Epub 2011 Dec 1.
Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma (HCC), but with limited efficacy. The present study aimed to assess the safety and efficacy of sorafenib combined with cryotherapy (cryoRx) for the treatment of advanced HCC. A total of 104 patients met the following criteria: advanced HCC without distant metastasis, presence of portal vein thrombosis, Child-Pugh class A or B and life expectancy of at least 12 weeks. All patients were randomly assigned to sorafenib and cryoRx (n=52) or sorafenib-alone (n=52) treatment groups. The primary end-point of the study was overall survival (OS). The secondary end-points included time to progression (TTP) and tolerability. Microvessel density (MVD) was assessed following immunostaining for CD34. In a median of 10.5 (4-26) months follow-up, the median OS was 12.5 months (95% CI 10.6-16.4) in the combination therapy vs. 8.6 months (7.3-10.4) in the sorafenib-alone (P=0.01) group. The median TTP was 9.5 months (8.4-13.5) in the combination therapy vs. 5.3 months (3.8-6.9) in the sorafenib alone (P=0.02) group. CryoRx was an independent factor associated with improved clinical outcomes of sorafenib for the treatment of advanced HCC. Patients with low intratumoral MVD receiving the combination therapy exhibited a significantly longer median TTP and OS compared to those receiving sorafenib. High intratumoral MVD was an independent predictor of poor responses to sorafenib for advanced HCC. Compared with previous reports of sorafenib-related adverse drug reactions (ADRs), cryoRx did not further increase the frequency and degree of sorafenib-related ADRs. In conclusion, compared to sorafenib alone, the addition of cryoRx to sorafenib significantly improves the clinical outcomes of sorafenib for the treatment of advanced HCC with acceptable tolerance and similar safety profiles as previously reported. High intratumoral MVD is predictive of poor responses to sorafenib in advanced HCC patients.
索拉非尼可延长晚期肝细胞癌（HCC）患者的生存期，但疗效有限。本研究旨在评估索拉非尼联合冷冻消融术（cryoRx）治疗晚期HCC的安全性和疗效。共有104例患者符合以下标准：无远处转移的晚期HCC、存在门静脉血栓形成、Child-Pugh A级或B级且预期生存期至少12周。所有患者被随机分为索拉非尼联合cryoRx组（n = 52）或单纯索拉非尼组（n = 52）。本研究的主要终点是总生存期（OS）。次要终点包括疾病进展时间（TTP）和耐受性。对CD34进行免疫染色后评估微血管密度（MVD）。在中位10.5（4 - 26）个月的随访中，联合治疗组的中位OS为12.5个月（95%CI 10.6 - 16.4），而单纯索拉非尼组为8.6个月（7.3 - 10.4）（P = 0.01）。联合治疗组的中位TTP为9.5个月（8.4 - 13.5），单纯索拉非尼组为5.3个月（3.8 - 6.9）（P = 0.02）。CryoRx是与索拉非尼治疗晚期HCC临床疗效改善相关的独立因素。与接受索拉非尼治疗的患者相比，接受联合治疗的瘤内MVD低的患者中位TTP和OS显著更长。瘤内MVD高是晚期HCC患者对索拉非尼反应不佳的独立预测因素。与先前关于索拉非尼相关药物不良反应（ADR）的报道相比，cryoRx并未进一步增加索拉非尼相关ADR的频率和程度。总之，与单纯索拉非尼相比，索拉非尼联合cryoRx显著改善了索拉非尼治疗晚期HCC的临床疗效，耐受性可接受，安全性与先前报道相似。瘤内MVD高可预测晚期HCC患者对索拉非尼反应不佳。
