肝细胞癌（hepatocellular carcinoma，HCC）是临床常见的消化系统恶性肿瘤之一，其起病隐匿，复发率及转移率高，治疗棘手，预后较差。索拉非尼是第1个被美国食品药品监督管理局批准应用于治疗临床不可切除HCC的多靶点激酶抑制剂，但是其单药疗效有限。近年来，国内外临床学者探索了索拉非尼联合其他化疗药物治疗晚期HCC的可行性，取得了一定进展。本文作者对上述研究进展作一综述。

[1] 王强凤,史肖华.肝细胞癌的新见解:从实验到临床[J].中国普通外科杂志,2015,24(1):1-9.
[2] 戴峰,朱西琪.索拉非尼在中晚期肝细胞肝癌治疗中的临床价值[J].东南大学学报:医学版,2016,35(1):106-108.
[3] QIN S,BAI Y,LIM H Y,et al.Randomized,multicenter,open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia[J].J Clin Oncol,2013,31(28):3501-3508.
[4] WILHELM S M,CARTER C,TANG L,et al.BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J].Cancer Res,2004,64(19):7099-7109.
[5] SHAABAN S,NEGM A,IBRAHIM E E,et al.Chemotherapeutic agents for the treatment of hepatocellular carcinoma:efficacy and mode of action[J].Oncol Rev,2014,8(1):246.
[6] ABOU-ALFA G K,JOHNSON P,KNOX J J,et al.Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma[J].JAMA,2010,304(19):2154-2160.
[7] ABOU-ALFA G K,NIEDZWIESKI D,KNOX J J,et al.Phase III randomized study of sorafenib plus doxorubicin versus sorafenib in patients with advanced hepatocellular carcinoma(HCC):CALGB 80802(Alliance)[C/OL].http://meetinglibrary.asco.org/content/171166-176.
[8] 孙家跃,左靖,金义光,等.吉西他滨的体内外抗肝癌作用研究[J].中国药房,2015,26(28):3941-3943.
[9] SRIMUNINNIMIT V,SRIURANPONG V,SUWANVECHO S,et al.Efficacy and safety of sorafenib in combination with gemcitabine in patients with advanced hepatocellular carcinoma:a multicenter,open-label,single-arm phase II study[J].Asia Pac J Clin Oncol,2014,10(3):255-260.
[10] PETRINI I,LENCIONI M,RICASOLI M,et al.Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma[J].Cancer Chemother Pharmacol,2012,69(3):773-780.
[11] ABDEL-RAHMAN O,ABDEL-WAHAB M,SHAKER M,et al.Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma[J].Med Oncol,2013,30(3):655.
[12] 隋忠国,薛宏伟,荆凡波,等.索拉非尼联合卡培他滨治疗肝细胞癌患者的临床研究[J].中国药房,2008,19(11):848-849.
[13] 陈德义,黄贤俊,陈雨,等.表柔比星、顺铂与优福定联合治疗晚期胃癌[J].肿瘤学杂志,2003,9(1):28-31.
[14] HSU C H,SHEN Y C,LIN Z Z,et al.Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma[J].J Hepatol,2010,53(1):126-31.
[15] 何丽平,翟凤钰.索拉非尼联合化疗治疗原发性肝癌的临床研究[J].中国医药科学,2013,3(22):63-64.
[16] LIU Y,YUE H,XU S,et al.First-line gemcitabine and oxaliplatin(GEMOX)plus sorafenib,followed by sorafenib as maintenance therapy,for patients with advanced hepatocellular carcinoma:a preliminary study[J].Int J Clin Oncol,2015,20(5):952-959.
[17] LLOVET J M,RICCI S,MAZZAFERRO V,et al.Sorafenib in advanced hepatocellular carcinoma[J].N Engl J Med,2008,359(4):378-390.
[18] CHENG A L,KANG Y K,CHEN Z,et al.Efficacy and safety of Sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phase III randomized,double-blind,placebo-controlled trial[J].Lancet Oncol,2009,10(1):25-34.
[19] JI Y X,ZHANG Z F,LAN K T,et al.Sorafenib in liver function impaired advanced hepatocellular carcinoma[J].Chin Med Sci J,2014,29(1):7-14.
[20] ADJEI A,MANDERKAR S,MARK R S,et al.A phase I study of BAY439006 and gefitinib in patients with refrectory or recurrent non-small cell lung cancer(NSCLC)[J].J Clin Oncol,2005,23:3067.
[21] McDERMOTT D F,MANOLA J,PINS M,et al.The BEST trial(E2804):a randomized phase II study of VEGF,RAF kinase,and mTOR combination targeted therapy(CTT)with bevacizumab(bev),sorafenib(sor),and temsirolimus(tem)in advanced renal cell carcinoma(RCC)[J].J Clin Oncol,2013,31(6):345.
[22] RYAN C W,GOLDMAN B H,LARA P N Jr,et al.Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma:a phase II study of the Southwest Oncology Group[J].J Clin Oncol,2007,25(22):3296-3301.
[23] AMARAVADI R K,SCHUCHTER L M,KRAMER A,et al.Preliminaryresults of a randomized study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma[J].J Clin Oncol,2006,24(18):8009.
[24] WELCH S,HIRTE H,SCHILDER R J,et al.Phase II study of sorafenib(BAY 43-9006)in combination with gemcitabine in recurrent epithelial ovarian cancer:a PMH phase II consortium trial[J].J Clin Oncol,2006,24(18):5084.