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阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展

龚晓斌 刘诗怡 夏天一 位华 陈万生

龚晓斌, 刘诗怡, 夏天一, 位华, 陈万生. 阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展[J]. 药学实践与服务, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
引用本文: 龚晓斌, 刘诗怡, 夏天一, 位华, 陈万生. 阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展[J]. 药学实践与服务, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
GONG Xiaobin, LIU Shiyi, XIA Tianyi, WEI Hua, CHEN Wansheng. Clinical application and research progress of apatinib in cancer treatment[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
Citation: GONG Xiaobin, LIU Shiyi, XIA Tianyi, WEI Hua, CHEN Wansheng. Clinical application and research progress of apatinib in cancer treatment[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002

阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展

doi: 10.3969/j.issn.1006-0111.2018.02.002
基金项目: 上海市科学技术委员会项目(13DZ1930600)

Clinical application and research progress of apatinib in cancer treatment

  • 摘要: 抗血管生成靶向治疗是近年来肿瘤治疗的研究热点。其中,血管新生抑制剂阿帕替尼是我国自主研制的1.1类新药。临床前研究和临床试验研究表明,阿帕替尼对胃癌、肺癌、乳腺癌等多种肿瘤均具有显著的抑制活性,其安全性和有效性良好。然而,阿帕替尼的相关研究显示,目前仍存在作用机制不十分明确等问题。因此,开展进一步研究以不断提高药物的安全性、有效性和经济性,是阿帕替尼广泛应用于临床的前提。总结阿帕替尼在国内外研究现状,从作用机制、药动学过程、临床疗效、安全性和生物标志物等角度进行归纳,探讨了近年来阿帕替尼研究的热点与争议问题,实现对阿帕替尼的临床应用前景展望。
  • [1] Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase Ⅲ trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction[J]. J Clin Oncol, 2016, 34(13):1448-1454.
    [2] Geng R, Li J. Apatinib for the treatment of gastric cancer[J]. Expert Opin Pharmacother, 2015, 16(1):117-122.
    [3] Tian S, Quan H, Xie C,et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo[J]. Cancer Sci, 2011, 102(7):1374-1380.
    [4] Li J, Qin S, Xu J,et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer:Results from a randomized, placebo-controlled, parallel-arm, phase Ⅱ trial[J]. J Clin Oncol, 2013, 31(26):3219-3225.
    [5] Roskoski R Jr. Vascular endothelial growth factor (VEGF) signaling in tumor progression[J]. Crit Rev Oncol Hematol, 2007, 62(3):179-213.
    [6] Folkman J, Merler E, Abernathy C,et al. Isolation of a tumor factor responsible for angiogenesis[J]. J Exp Med, 1971, 133(2):275-288.
    [7] Sia D, Alsinet C, Newell P,et al. VEGF signaling in cancer treatment[J]. Curr Pharm Des, 2014, 20(17):2834-2842.
    [8] Muller YA, Li B, Christinger HW,et al. Vascular endothelial growth factor:crystal structure and functional mapping of the kinase domain receptor binding site[J].Proc Natl Acad Sci USA, 1997, 94(14):7192-7197.
    [9] Holmes K, Roberts OL, Thomas AM,et al. Vascular endothelial growth factor receptor-2:structure, function, intracellular signalling and therapeutic inhibition[J]. Cell signal, 2007, 19(10):2003-2012.
    [10] Olsson AK, Dimberg A, Kreuger J,et al. VEGF receptor signalling-in control of vascular function[J]. Nat Rev Mol Cell Biol, 2006, 7(5):359-371.
    [11] Vesely DL. Family of peptides synthesized in the human body have anticancer effects[J]. Anticancer Res, 2014, 34(4):1459-1466.
    [12] Koch S, Tugues S, Li X,et al. Signal transduction by vascular endothelial growth factor receptors[J]. Biochem J, 2011, 437(2):169-183.
    [13] Peng S, Zhang Y, Peng H,et al. Intracellular autocrine VEGF signaling promotes EBDC cell proliferation, which can be inhibited by apatinib[J]. Cancer Lett, 2016, 373(2):193-202.
    [14] Ji G, Hong L, Yang P. Successful treatment of advanced malignant fibrous histiocytoma of the right forearm with apatinib:a case report[J]. Onco Targets Ther, 2016, 9:643-647.
    [15] Zhou N, Liu C, Hou H,et al. Response to apatinib in chemotherapy-failed advanced spindle cell breast carcinoma[J]. Oncotarget, 2016, 7(44):72373-72379.
    [16] Peng H, Zhang Q, Li J,et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma[J]. Oncotarget, 2016, 7(13):17220-17229.
    [17] Ilson DH. Targeting the vascular endothelial growth factor pathway in gastric cancer:a hit or a miss?[J]. J Clin Oncol, 2016, 34(13):1431-1432.
    [18] Moehler M, Mueller A, Hartmann JT,et al. An open-label, multicentre biomarker-oriented AIO phase Ⅱ trial of sunitinib for patients with chemo-refractory advanced gastric cancer[J]. Eur J Cancer, 2011, 47(10):1511-1520.
    [19] Bang YJ, Kang YK, Kang WK,et al. Phase Ⅱ study of sunitinib as second-line treatment for advanced gastric cancer[J]. Invest New Drugs, 2011, 29(6):1449-1458.
    [20] Yi JH, Lee J, Lee J,et al. Randomised phase Ⅱ trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum[J]. Br J Cancer, 2012, 106(9):1469-1474.
    [21] Martin-Richard M, Gallego R, Pericay C,et al. Multicenter phase Ⅱ study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD study[J]. Invest New Drugs, 2013, 31(6):1573-1579.
    [22] Sun W, Powell M, O'Dwyer PJ,et al. Phase Ⅱ study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma:ECOG 5203[J]. J Clin Oncol, 2010, 28(18):2947-2951.
    [23] Ohtsu A, Shah MA, Van Cutsem E,et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer:a randomized, double-blind, placebo-controlled phase Ⅲ study[J]. J Clin Oncol, 2011, 29(30):3968-3976.
    [24] Shen L, Li J, Xu J,et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer:randomized, double-blind, phase Ⅲ study (AVATAR study)[J]. Gastric Cancer, 2015, 18(1):168-176.
    [25] Fuchs CS, Tomasek J, Yong CJ,et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD):an international, randomised, multicentre, placebo-controlled, phase 3 trial[J]. Lancet, 2014, 383(9911):31-39.
    [26] Wilke H, Muro K, Van Cutsem E,et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW):a double-blind, randomised phase 3 trial[J]. Lancet Oncol, 2014, 15(11):1224-1235.
    [27] Tarazona N, Gambardella V, Huerta M,et al. Personalised treatment in gastric cancer:myth or reality?[J]. Curr Oncol Rep, 2016, 18(7):41.
    [28] Park DJ, Thomas NJ, Yoon C,et al. Vascular endothelial growth factor a inhibition in gastric cancer[J]. Gastric Cancer, 2015, 18(1):33-42.
    [29] Van Cutsem E, de Haas S, Kang YK,et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer:a biomarker evaluation from the AVAGAST randomized phase Ⅲ trial[J]. J Clin Oncol, 2012, 30(17):2119-2127.
    [30] Tong XZ, Wang F, Liang S,et al. Apatinib (YN968D1) enhances the efficacy of conventional chemotherapeutical drugs in side population cells and ABCB1-overexpressing leukemia cells[J]. Biochem Pharmacol, 2012, 83(5):586-597.
    [31] Mi YJ, Liang YJ, Huang HB,et al. Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters[J]. Cancer Res, 2010, 70(20):7981-7991.
    [32] Ding J, Chen X, Gao Z,et al. Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans[J]. Drug Metab Dispos, 2013, 41(6):1195-1210.
    [33] Li J, Zhao X, Chen L,et al. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies[J]. BMC Cancer, 2010, 10:529.
    [34] Lin D, Wang Z, Li J,et al. The effect of apatinib on the metabolism of carvedilol both in vitro and in vivo[J]. Pharmacology, 2016, 97(1-2):31-37.
    [35] Yu M, Gao Z, Dai X,et al. Population pharmacokinetic and covariate analysis of apatinib, an oral tyrosine kinase inhibitor, in healthy volunteers and patients with solid tumors[J]. Clin Pharmacokinet, 2017, 56(1):65-76.
    [36] Hu X, Cao J, Hu W,et al. Multicenter phase Ⅱ study of apatinib in non-triple-negative metastatic breast cancer[J]. BMC Cancer, 2014, 14:820.
    [37] Hu X, Zhang J, Xu B,et al. Multicenter phase Ⅱ study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer[J]. Int J Cancer, 2014, 135(8):1961-1969.
    [38] Fan M, Zhang J, Wang Z,et al. Phosphorylated VEGFR2 and hypertension:potential biomarkers to indicate VEGF-dependency of advanced breast cancer in anti-angiogenic therapy[J]. Breast Cancer Res Treat, 2014, 143(1):141-151.
    [39] Zhang L, Shi M, Huang C,et al. A phase Ⅱ, multicenter, placebo-controlled trial of apatinib in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after two previous treatment regimens[J]. J Clin Oncol,2012, 30(15_suppl):7548.
    [40] Qin S. Apatinib in Chinese patients with advanced hepatocellular carcinoma:a phase Ⅱ randomized, open-label trial[J]. J Clin Oncol, 2014, 32(15_suppl):4019.
    [41] Li XF, Tan YN, Cao Y,et al. A case report of gastrointestinal hemorrhage and perforation during apatinib treatment of gastric cancer[J]. Medicine (Baltimore), 2015, 94(39):e1661.
    [42] Ding C, Zhang C, Zhang M,et al. Multitarget inhibitors derived from crosstalk mechanism involving VEGFR2[J]. Future Med Chem, 2014, 6(16):1771-1789.
    [43] Loges S, Mazzone M, Hohensinner P,et al. Silencing or fueling metastasis with VEGF inhibitors:Antiangiogenesis revisited[J]. Cancer Cell, 2009, 15(3):167-170.
    [44] Roviello G, Ravelli A, Fiaschi AI,et al. Apatinib for the treatment of gastric cancer[J]. Expert Rev Gastroenterol Hepatol, 2016, 10(8):887-892.
    [45] Lin C, Wang S, Xie W,et al. Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway[J]. Oncotarget, 2016, 7(37):59236-59244.
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阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展

doi: 10.3969/j.issn.1006-0111.2018.02.002
    基金项目:  上海市科学技术委员会项目(13DZ1930600)

摘要: 抗血管生成靶向治疗是近年来肿瘤治疗的研究热点。其中,血管新生抑制剂阿帕替尼是我国自主研制的1.1类新药。临床前研究和临床试验研究表明,阿帕替尼对胃癌、肺癌、乳腺癌等多种肿瘤均具有显著的抑制活性,其安全性和有效性良好。然而,阿帕替尼的相关研究显示,目前仍存在作用机制不十分明确等问题。因此,开展进一步研究以不断提高药物的安全性、有效性和经济性,是阿帕替尼广泛应用于临床的前提。总结阿帕替尼在国内外研究现状,从作用机制、药动学过程、临床疗效、安全性和生物标志物等角度进行归纳,探讨了近年来阿帕替尼研究的热点与争议问题,实现对阿帕替尼的临床应用前景展望。

English Abstract

龚晓斌, 刘诗怡, 夏天一, 位华, 陈万生. 阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展[J]. 药学实践与服务, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
引用本文: 龚晓斌, 刘诗怡, 夏天一, 位华, 陈万生. 阿帕替尼在恶性肿瘤治疗中的临床应用与研究进展[J]. 药学实践与服务, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
GONG Xiaobin, LIU Shiyi, XIA Tianyi, WEI Hua, CHEN Wansheng. Clinical application and research progress of apatinib in cancer treatment[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
Citation: GONG Xiaobin, LIU Shiyi, XIA Tianyi, WEI Hua, CHEN Wansheng. Clinical application and research progress of apatinib in cancer treatment[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(2): 103-107,130. doi: 10.3969/j.issn.1006-0111.2018.02.002
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