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中国患者肾细胞癌的靶向治疗:聚焦依维莫司

Targeted therapies for renal cell carcinoma in Chinese patients: focus on everolimus.

作者信息

Tan Xiaojie, Liu Yan, Hou Jianguo, Cao Guangwen

机构信息

Department of Epidemiology, Second Military Medical University, Shanghai, People's Republic of China.

Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.

出版信息

Onco Targets Ther. 2015 Jan 29;8:313-21. doi: 10.2147/OTT.S64660. eCollection 2015.

Abstract

Renal cell carcinoma (RCC) is the most common type of cancer arising from the kidney, with a male to female ratio of 2:1. The incidence of RCC is rising. In males, it was the seventh most common cancer in the People's Republic of China in 2012. RCC is resistant to radiotherapy and chemotherapy, but approximately 20% of patients with advanced RCC respond to immunotherapy. Novel therapies targeting angiogenesis and signaling pathways have been proven to be effective for advanced or metastatic RCC in Western countries. Due to the heterogeneity of RCC between races, it is necessary to have an overview of targeted therapies, especially everolimus, for patients with advanced RCC in the People's Republic of China. Three targeted therapeutic agents have been approved in Mainland China for the treatment of patients with advanced RCC, ie, two tyrosine kinase inhibitors (sorafenib and sunitinib) and one mammalian target of rapamycin (mTOR) inhibitor (everolimus). Compared with Western patients with advanced or metastatic RCC, Chinese patients with the same disease respond better to sorafenib and sunitinib as first-line targeted therapy, but sunitinib has a relatively higher risk of toxicity. Everolimus, an mTOR inhibitor that can be administered orally, is well tolerated and acceptable to Chinese patients. Everolimus has competitive advantages as second-line targeted treatment for Chinese patients with advanced RCC who are resistant to first-line tyrosine kinase inhibitors. Despite a lack of noninferiority when compared with sunitinib as first-line therapy, the sunitinib-everolimus paradigm is still recommended as standard therapy for patients with advanced RCC. Although most studies of targeted therapies for advanced RCC have obvious limitations, such as small sample size and retrospective design, up-to-date evidence indicates that everolimus would be an ideal agent as second-line targeted treatment for advanced or metastatic RCC in the People's Republic of China.

摘要

肾细胞癌(RCC)是起源于肾脏的最常见癌症类型,男女比例为2:1。RCC的发病率正在上升。在男性中,它是2012年中华人民共和国第七大常见癌症。RCC对放疗和化疗具有抗性,但约20%的晚期RCC患者对免疫疗法有反应。在西方国家,针对血管生成和信号通路的新型疗法已被证明对晚期或转移性RCC有效。由于不同种族间RCC的异质性,有必要对中华人民共和国晚期RCC患者的靶向治疗,尤其是依维莫司,进行概述。中国大陆已批准三种靶向治疗药物用于治疗晚期RCC患者,即两种酪氨酸激酶抑制剂(索拉非尼和舒尼替尼)和一种哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂(依维莫司)。与西方晚期或转移性RCC患者相比,患有相同疾病的中国患者作为一线靶向治疗对索拉非尼和舒尼替尼反应更好,但舒尼替尼的毒性风险相对较高。依维莫司是一种可口服的mTOR抑制剂,中国患者对其耐受性良好且可接受。对于对一线酪氨酸激酶抑制剂耐药的中国晚期RCC患者,依维莫司作为二线靶向治疗具有竞争优势。尽管与舒尼替尼作为一线治疗相比缺乏非劣效性,但舒尼替尼-依维莫司模式仍被推荐作为晚期RCC患者的标准治疗。尽管大多数针对晚期RCC的靶向治疗研究存在明显局限性,如样本量小和回顾性设计,但最新证据表明,依维莫司将是中华人民共和国晚期或转移性RCC二线靶向治疗的理想药物。

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