Advances in drug research for advanced hepatocellular carcinoma
ZHANG Wenwen1,2 ZHENG Xizi3 ZHENG Xiaohong1,2 LIU Xiaodong1,2
1.College of Pharmacy, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China;
2.Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing 401331, China;
3.Department of Pharmacy, Changshou District Hospital of Traditional Medicine, Chongqing 401220, China
Abstract：Hepatocellular carcinoma is one of the most common and fatal cancers in the world. It is the fourth most common malignant tumor and the third leading cause of death in China. Due to high rate of intermediate or late diagnosis, the majority of patients have no opportunity to undergo potentially curative surgery. Moreover, the overall efficacy and safety of local treatment, radiotherapy, systemic chemotherapy and “gold standard” Sorafenib targeted therapy are not satisfactory, more safe and effective treatment means and drugs are urgently needed. Systemic chemotherapy regimens containing Oxaliplatin are able to improve the efficacy of Asia Pacific patients with advanced liver cancer, but the survival benefit is limited. The success of the new molecular targeted drugs Levatinib and Regofenib in the first and second line treatment provide new treatment options for patients. Immunotherapy, represented by the checkpoint inhibitors Nivolumab and Pembrolizumab, has shown great advantages in the clinical study of advanced liver cancer, opening a new era of immunotherapy for liver cancer. This article reviews the latest development and trends of advanced liver cancer drugs.
[1] Chen W，Zheng R，Baade PD，et al. Cancer statistics in China，2015 [J]. CA Cancer J Clin，2016，66（2）：115-132.
[2] Heimbach JK，Kulik LM，Finn RS，et al. AASLD guidelines for the treatment of hepatocellular carcinoma [J]. Hepatology，2018，67（1）：358-380.
[3] Yen Y，Lim DW，Chung V，et al. Phase Ⅱ study of oxaliplatin in patients with unresectable，metastatic，or recurrent hepatocellular cancer：a california cancer consortium trial [J]. Am J Clin Oncol，2008，31（4）：317-322.
[4] Qin S，Bai Y，Lim HY，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.
[5] Grazie ML，Biagini MR，Tarocchi M，et al. Chemotherapy for hepatocellular carcinoma：The presentand the future [J]. World J Hepatol，2017，9（21）：907-920.
[6] Woo HY，Yoo SY，Heo J. New chemical treatment options in second-line hepatocellular carcinoma：what to do when sorafenib fails [J]. Expert Opin Pharmacother，2017，18（1）：35-44.
[7] Bruix J，Qin S，Merle P，et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment （RESORCE）：a randomised，double-blind，placebo-controlled，phase 3 trial [J]. Lancet，2017，389（10 064）：56-66.
[8] Kudo M，Finn RS，Qin S，et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma：a randomised phase 3 non-inferiority trial [J]. Lancet，2018，391（10 126）：1163-1173.
[9] Waller LP，Deshpande V，Pyrsopoulos N. Hepatocellular carcinoma：a comprehensive review [J]. World J Hepatol，2015，7（26）：2648-2663.
[10] Kim HY，Park JW. Current immunotherapeutic strategies in hepatocellular carcinoma：recent advances and future directions [J]. Therap Adv Gastroenterol，2017，10（10）：805-814.
[11] Aerts M，Benteyn D，Van Vlierberghe H，et al. Current status and perspectives of immune-based therapies for hepatocellular carcinoma [J]. World J Gastroenterol，2016，22（1）：253-261.
[12] Sia D，Jiao Y，Martinez-Quetglas I，et al. Identification of an immune-specific class of hepatocellular carcinoma based on molecular features [J]. Gastroenterology，2017， 153（3）：812-826.
[13] El-Khoueiry AB，Sangro B，Yau T，et al. Nivolumab in patients with advanced hepatocellular carcinoma （CheckMate 040）：an open-label，non-comparative，phase 1/2 dose escalation and expansion trial [J]. Lancet，2017，389（10 088）：2492-2502.
[14] Zhu AX，Finn RS，Edeline J，et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib （KEYNOTE-224）：a non-randomised，open-label phase 2 trial [J]. Lancet Oncol，2018，19（7）：940-952.
[15] Sangrob B，Gomez-Martin M，de la Mata M，et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C [J]. J Hepatol，2013，59（1）：81-88.
[16] Duffy AG，Ulahannan SV，Makorova-Rusher O，et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma [J]. J Hepatol，2017，66（3）：545-551.
[17] Ager A，Watson HA，Wehenkel SC，et al. Homing tosolid cancers：a vascular checkpoint in adoptive cell therapy using CAR T-cells [J]. Biochem Soc Trans，2016，44（2）：377-385.
[18] Liu H，Xu Y，Xiang J，et al. Targeting Alpha Fetoprotein （AFP）-MHC complex with CART-Cell therapy for liver cancer [J]. Clin Cancer Res，2017，23（2）：478-488.
[19] Pan K，Li YQ，Wang W，et al. The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients [J]. Ann Surg Oncol，2013，20（13）：4305-4311.
[20] Lee JH，Lee JH，Lim YS，et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma [J]. Gastroenterology，2015，148（7）：1383-1391.
[21] Zerbini A，Pilli M，Laccabue D，et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response [J]. Gastroenterology，2010， 138（5）：1931-1942.
2019, Vol. 16 
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