Luo Cong, Shen Jiayu, Ying Jieer, Fang Xianhua, Wang Xiaohong, Fu Zhixuan, Liu Peng
Department of Abdominal Oncology, Zhejiang Cancer Hospital.
The Second Clinical Medical College, Zhejiang Chinese Medical University.
Onco Targets Ther. 2017 Sep 14;10:4553-4557. doi: 10.2147/OTT.S146409. eCollection 2017.
Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2) and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ) is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with mutation.
恶性黑色素瘤是一种死亡率高、易转移且预后较差的恶性疾病。近几十年来，随着新型药物的研发，治疗格局正在迅速改变，如抗程序性死亡蛋白1（PD-1）药物、抗细胞毒性T淋巴细胞相关抗原4（CTLA-4）药物和BRAF抑制剂。然而，由于这些新型药物大多非常昂贵，并非所有患者都能负担得起。阿帕替尼是一种新型口服小分子酪氨酸激酶抑制剂，靶向血管内皮生长因子受体2（VEGFR-2）的细胞内结构域，对Ret、c-KIT和c-src也可能有效。替莫唑胺（TMZ）是第二代烷化剂，是用于治疗黑色素瘤的细胞毒性药物。在本研究中，我们报告了1例转移性黑色素瘤患者，对阿帕替尼/TMZ联合治疗反应良好，无进展生存期超过1年。该患者CD117、VEGFR-3高表达且第11外显子存在突变，提示阿帕替尼可能通过抑制VEGFR和c-KIT诱导临床反应。阿帕替尼/TMZ联合治疗可能是治疗存在 突变的晚期黑色素瘤的新选择。
