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中华口腔医学研究杂志(电子版)

中华口腔医学研究杂志(电子版) ›› 2020, Vol. 14 ›› Issue (05) : 325 -329. doi: 10.3877/cma.j.issn.1674-1366.2020.05.009

所属专题： 口腔医学； 文献；

综述

安罗替尼的研究现状及其应用于晚期口腔鳞状细胞癌的治疗前景
楚晨1, 孙艳1,†(), 尚伟2, 张晓春3, 葛胜优2   
  1. 1. 青岛大学附属医院口腔内科　266000；青岛大学口腔医学院　266000
    2. 青岛大学口腔医学院　266000；青岛大学附属医院口腔颌面外科　266000
    3. 青岛大学附属医院肿瘤精准医学中心　266000
  • 收稿日期:2020-02-21 出版日期:2020-10-01
  • 通信作者: 孙艳

The current states of anlotinib and its prospect in advanced oral squamous cell carcinoma

Chen Chu1, Yan Sun1,†(), Wei Shang2, Xiaochun Zhang3, Shengyou Ge2   

  1. 1. Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; School of Stomatology of Qingdao University, Qingdao 266000, China
    2. School of Stomatology of Qingdao University, Qingdao 266000, China; Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
    3. Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
  • Received:2020-02-21 Published:2020-10-01
  • Corresponding author: Yan Sun
  • About author:
    Corresponding author: Sun Yan, Email:
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引用本文：

楚晨, 孙艳, 尚伟, 张晓春, 葛胜优. 安罗替尼的研究现状及其应用于晚期口腔鳞状细胞癌的治疗前景[J]. 中华口腔医学研究杂志(电子版), 2020, 14(05): 325-329.

Chen Chu, Yan Sun, Wei Shang, Xiaochun Zhang, Shengyou Ge. The current states of anlotinib and its prospect in advanced oral squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2020, 14(05): 325-329.

晚期口腔鳞状细胞癌（OSCC）患者生存期短，预后较差。由于手术效果不佳、耐药性、不良反应等原因，亟需更安全有效的新型化疗药物以提高晚期OSCC患者生存质量。安罗替尼（anlotinib）是我国自主研发的一种口服多靶点小分子酪氨酸激酶抑制剂，能够与多种血管生成因子受体靶向结合，抑制肿瘤血管生成，干扰肿瘤细胞增殖等生物学行为，有望成为多种晚期恶性肿瘤治疗药物。本文对安罗替尼的作用机制、研究现状及其应用于晚期OSCC术后化疗的治疗前景等进行分析综述。

关键词: 癌，鳞状细胞, 血管内皮生长因子类, 安罗替尼, 血管生成, 化疗

Patients with advanced oral squamous cell carcinoma often show short survival time and poor prognosis. Because of the poor efficacy of surgery, drug resistance and adverse events etc., the quality of life of these patients are required to improved by novel drugs with safety and efficacy. Anlotinib is a domestic small-molecule tyrosine kinase inhibitor, which has been presently regarded as a potential medicine for multiple advanced malignances. It targets multiple angiogenetic factor receptors to suppress the angiogenesis and inhibit partial functions of tumor cells. This review will focus on the mechanism, research status of anlotinib and its potential efficacy in advanced oral squamous cell carcinoma.

Key words: Carcinoma, squamous cell, Vasculare endothelial growth factors, Anlotinib, Angiogenesis, Chemotherapy
图1 安罗替尼作用机制[5]
表1 有关安罗替尼治疗晚期恶性肿瘤的临床试验
临床试验注册号 研究阶段 治疗方案顺序 对照组 人数 PFS[月，中位数(95% CI)] OS[月，中位数(95% CI)] ORR(%) 治疗相关
调整剂量人数(%) 死亡人数(%)
晚期非小细胞肺癌 ? ? ? ? ? ? ? ? ?
? NCT01924195[18] Ⅱ期 3线及以上 安慰剂 117 4.8(3.5 ~ 6.4)VS 1.2(0.7 ~ 1.6), P<0.001 9.3(6.8 ~ 15.1)VS 6.3(4.3 ~ 10.5), P = 0.232 10.0 VS 0.0,P = 0.028 10.0 0.0
? NCT02388919[19] Ⅲ期 3线及以上 安慰剂 439 5.4(4.4 ~ 5.6)VS 1.4(1.1 ~ 1.5), P<0.001 9.6(8.2 ~ 10.6)VS 6.3(5.0 ~ 8.1), P = 0.002 9.2 VS 0.7,P<0.001 8.9 -
晚期软组织肉瘤 ? ? ? ? ? ? ? ? ?
? NCT01878448[20] Ⅱ期 NR - 166 5.6(4.4 ~ 7.7) 12.0(11.0 ~ 16.0) 13.0 14.5 0.0
晚期髓样甲状腺癌 ? ? ? ? ? ? ? ? ?
? NCT01874873[22] Ⅱ期 NR - 58 - - 56.9 20.7 -
转移性肾细胞癌 ? ? ? ? ? ? ? ? ?
? NCT02072031[24] Ⅱ期 1线 Sunitinib 133 17.5 VS 16.6,P>0.05 30.9 VS 30.5,P>0.05 30.3 VS 27.9,P>0.05 7.8 VS 16.3，P = 0.14 -
表2 安罗替尼与其他酪氨酸酶抑制剂（TKI）比较
药品 不同点 相似点
安罗替尼 1.对VEGFR-2/3选择性较强，抑制肿瘤血管生成能力较强 1.作用机制相似，与VEGFR等血管生成因子受体结合，抑制肿瘤血管生成2.结合靶点较多，干扰多条信号通路，不良反应（高血压、手足综合征等）较多
2.不良反应大多可缓解，腹泻发生率相对较低
3.易发生血脂升高、甘油三酯升高，需监测血压、血脂等指标
索拉菲尼、舒尼替尼等 1.与VEGFR结合能力相对较弱，抑制肿瘤血管生成能力较弱
2.腹泻发生率相对较高
3.血脂升高、甘油三酯升高发生率相对较低
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