索拉菲尼联合沙利度胺治疗原发性肝癌的临床研究

Clinical trial of sorafenib combined with thalidomide in the treatment of patients with primary liver cancer

目的研究索拉菲尼联合沙利度胺对原发性肝癌患者的影响。方法将原发性肝癌患者随机分为对照组34例和试验组34例。对照组用肝动脉介入化疗方案,予以顺铂80~100 mg+5-氟尿嘧啶1.0 g+盐酸多柔比星40~60 mg+丝裂霉素10 mg;在对照组治疗基础上,试验组予以沙利度胺片100 mg,qd,1周后增至200 mg,qd,睡前顿服;予以甲苯磺酸索拉非尼片400 mg,qd,口服。2组患者均治疗12周。用免疫组化S-P法测定肝癌组织Survivin蛋白表达水平;用化学发光免疫法测定血清糖类抗原125(CA125)水平;用酶联免疫吸附试验(ELISA)测定血清血管内皮生长因子(VEGF)水平。观察与比较2组的临床疗效和药物不良反应(ADR)发生情况。结果治疗后,试验组和对照组的总有效率分别为88.24%(30例/34例)和67.65%(23例/34例),组间比较差异有统计学意义(P<0.05)。这2组的Survivin蛋白阳性表达率分别为29.41%(10例/34例)和52.94%(18例/34例);这2组的CA125分别为(26.85±10.07),(37.51±11.34)k U·L^(-1);这2组的VEGF分别为(178.93±20.43),(210.10±22.57)pg·m L^(-1),组间比较差异均有统计学意义(均P<0.05)。这2组的第3年生存率分别为61.76%(21例/34例)和41.18%(14例/34例),差异有统计学意义(P<0.05);这2组的ADR发生率分别为8.82%(3例/34),5.88%(2例/34例),组间差异无统计学意义(P>0.05)。结论索拉菲尼联合沙利度胺治疗原发性肝癌的临床疗效确切,能降低Survivin蛋白及CA125表达,提高生存率,且不加重ADR,安全有效。

Objective To investigate the effects of sorafenib combined with thalidomide in the treatment of patients with primary liver cancer.Methods The patients with primary liver cancer were randomly divided into control group and treatment group with 34 cases in each. The control group was treated with hepatic artery interventional chemotherapy： cisplatin 80^（-1）00 mg ＋ 5-fluorouracil 1. 0 g ＋ doxorubicin hydrochloride40-60 mg ＋ mitomycin 10 mg; on the basis of control group,the treatment group was treated with thalidomide tablets 100 mg,qd,then increased to 200 mg after 1 week,qd,orally,before bedtime; sorafenib tosylate tablets 400 mg,qd,orally. Patients of two groups were treated for12 weeks. The expression of Survivin protein of liver tissue was detected by immunohistochemical S-P method. The level of the carbohydrate antigen 125（ CA125） was detected by immunochemiluminescence. The level of vascular endothelial growth factor（ VEGF） was detected by enzymelinked immunosorbent assay. The clinical efficacy and the occurrence of adverse drugs reaction（ ADR） were compared between the 2 groups. Results After treatment,the total effective rates of treatment group and control group were respectively 88. 24%（ 30 cases/34 cases） and 67. 65%（ 23 cases/34 cases）,there was a significant difference between groups（ P 0. 05）. The positive expression rate of Survivin protein in the 2 groups were respectively 29. 41%（ 10 cases/34 cases） and 52. 94%（ 18 cases/34 cases）; the CA125 level in the 2 groups were respectively（ 26. 85 ± 10. 07）,（ 37. 51 ± 11. 34） k U·L^（-1）; the VEGF level in the 2 groups were respectively（ 178. 93 ± 20. 43）,（ 210. 10 ± 22. 57）pg·m L^（-1）,there was a significant difference in two groups（ all P 0. 05）. The 3 years survival rate of 2 groups were respectively 61. 76%（ 21 cases/34 cases） and 41. 18%（ 14 cases/34 cases）,there was a significant difference in 2 groups（ P 0. 05）. The incidence of ADR in the 2 groups were 8. 82%（ 3 cases/34 cases）,5. 88%（ 2 cases/34 cases）,without significant difference（ P 0. 05）. Conclusion Sorafenib combined with thalidomide had definite clinical efficacy for the treatment of patients with primary liver cancer,which can reduce the expression of Survivin protein and CA125,improve the survival rate,without aggravating the ADR.