TACE联合索拉非尼治疗不能手术切除肝细胞肝癌50例

Ttransarterial chemoembolization combined with sorafenib for inoperable hepatocellular carcinoma: a clinical analysis of 50 cases

目的观察经动脉化疗栓塞术（TACE）联合索拉非尼治疗不能手术切除肝细胞肝癌（HCC）的临床疗效和不良反应，探索影响疗效的相关因素，评价联合治疗的安全性。方法对2008年7月至2011年5月不能手术切除的50例HCC患者行TACE联合索拉非尼治疗。主要观察指标为至疾病进展时间（time to progression，TTP）和索拉非尼的不良反应，次要观察指标为总生存时间（overall survival。0S）。结果截至2011年12月，50例患者中位随访时间310d，按照mRECIST标准评价．34例患者病变进展，中位TTP（mTTP）为210d（95％CI：159-261d），36例患者存活，未达到中位OS（mOS）。治疗前患者无肝外转移的mTTP为316d，有肝外转移的mTTP为172d，Kaplan—Meier法分析差异有统计学意义（X^2=10．653，P=0．001）；COX回归法单因素分析风险比为0．321，（95％CI：0．157—0．658，P=0．002）。50例患者中46例服用索拉非尼出现不同程度的不良反应，主要包括皮肤反应29例（58％）、乏力27例（54％）、腹泻20例（40％）、高血压19例（38％）等，共出现3级不良反应32例次，未出现4级不良反应。联合治疗前患者TACE治疗平均间隔时间69d，联合治疗后TACE治疗平均间隔时间为112d。结论TACE联合索拉非尼治疗不能手术切除HCC有一定疗效，尤其是治疗前无肝外转移的患者可以明显延长TTP，安全性好，延长了患者TACE治疗间隔时间。尽早联合使用索拉非尼，可提高疗效，使患者更多的生存获益。

Objective ＇ To evaluate the efficacy and adverse reactions of transarterial chemoembolization （TACE） combined with sorafenib in treating inoperable hepatocellular carcinoma （HCC）, to discuss the relevant factors that affect the efficacy, and to assess the safety of the combination therapy. Methods During the period from July 2008 to May 2011, in authors＇ hospital TACE combined with sorafenib therapy was carried out in a total of 50 patients with inoperable HCC. The main observation indexes were the time to progression （TIP） and adverse reactions caused by sorafenib, and the secondary observation index was the overall survival time （OS）. Results Up to December 2011, the median follow-up time of the 50 patients was 310 days, and according to mRECIST criteria 34 patients belonged to disease progression with the median time to progression （mTTP） of 210 days （95% confidence interval： 159,381 - 260.619 days）. Thirty-six patients survived and did not reach the median overall survival time （mOS）. The mTTP of patients having no extra-hepatic metastases before the treatment was 316 days, while the mITP of patients having extra- hepatic metastases before the treatment was 172 days. By using Kaplan- Meier analysis the difference between the two groups was statistically significant （chi- square = 10.653, P = 0.001 ）. Cox＇ssingle- factor regression analysis showed that the hazard ratio （HR） was 0.321 （95% confidence interval： 0.157 to 0.658, P = 0.002）. Of 50 patients, different degrees ofadverse effects occurred in 46 after taking sorafenib, which mainly included hand-foot syndrome （n = 29, 58%）, fatigue （n = 27, 54%）, diarrhea （n = 20, 40%） and hypertension （n = 19, 38%）. Thirty-two adverse effects were of Grade 3, and no Grade 4 adverse effect occurred. Before combination therapy the average TACE treatment interval was 69 days, while after combination therapy the average TACE treatment interval became 112 days. Conclusion TACE combined with sorafenib is very safe and effective for inoperable HCC with satisfactory clinical results, especially for patients who have no extra-hepatic metastases. This therapy can significantly elongate TTP as well as the TACE treatment interval. Combination use of TACE and sorafenib should be employed as early as possible so as to improve the prognosis, thus the patients can get more survival benefits.（J Intervent Radio1, 2013, 22： 381-386）