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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

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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
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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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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

  • 第二军医大学附属长征医院药材科, 上海 200003

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

  • Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

  • 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。
    Abstract: Antiangiogenic target therapy has been a hot topic in cancer treatment recently. Apatinib is a category 1.1 new medication developed domestically. It effectively inhibits angiogenic and exhibits promising anti-tumor activity in preclinical studies. Apatinib has been successfully applied in clinical trials of multiple malignancies, such as gastric cancer, lung cancer and breast cancer with satisfactory safety and efficacy profile. However, its mechanism of action is still not fully understood. Further researches should be carried on to improve its safety, effectiveness and marketability. This review summarized the mechanism of action, pharmacokinetics, clinical efficacy, safety and biomarkers, discussed the recent progress, hot issues and clinical prospects of apatinib,
  • [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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  • 收稿日期:  2017-11-05
  • 修回日期:  2018-01-09

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
  • 第二军医大学附属长征医院药材科, 上海 200003
    • 基金项目:  上海市科学技术委员会项目（13DZ1930600）
  • 收稿日期: 2017-11-05
  • 修回日期: 2018-01-09

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
shu
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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