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日本转移性肾细胞癌的药物治疗现状。

Current status of pharmacotherapy against metastatic renal cell carcinoma in Japan.

机构信息

Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

Int J Urol. 2012 Apr;19(4):284-95. doi: 10.1111/j.1442-2042.2012.02962.x.

Abstract

So far, metastatic renal cell carcinoma has been one of the most treatment-resistant cancers. The extensive use of cytokines, such as interferon-α and interleukin-2, were carried out for metastatic renal cell carcinoma. However, significant advances in understanding the molecular mechanisms underlying renal cell carcinoma have led to the development of molecular target-based drugs, which were desperately awaited for a long time, and now two types of molecular target-based drugs are available. Two vascular endothelial growth factor receptor tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have been approved and available in Japan. The molecular target-based drugs have unique and characteristic adverse events, whose profile are not well understood in Japanese patients, because most of the clinical trials were carried out in Europe and America. In contrast, immunotherapy is being reconsidered in the selection of more appropriate patients or as a combined treatment form with other drugs, because of few complete responses obtained and unexpected adverse events by molecular targeted treatments. We have several molecular targeted-drugs available at present and will have more, and we will actually use these drugs in various clinical settings, such as the presurgical setting, the adjuvant setting, sequential administration and combined administration, in addition to cytokines. Therefore, we need more elaborate studies to obtain the optimal treatment methods to maximize the effect of such agents to extend overall survival while maintaining quality of life of metastatic renal cell carcinoma patients. In this article, we reviewed the issues related to the current status of pharmacotherapy available for metastatic renal cell carcinoma.

摘要

到目前为止,转移性肾细胞癌一直是最难治疗的癌症之一。曾广泛使用细胞因子,如干扰素-α和白细胞介素-2,来治疗转移性肾细胞癌。然而,对肾细胞癌分子机制的深入理解,导致了靶向药物的发展,这是长期以来人们迫切需要的,现在有两种靶向药物可供选择。两种血管内皮生长因子受体酪氨酸激酶抑制剂和两种哺乳动物雷帕霉素靶蛋白抑制剂已在日本获得批准和应用。靶向药物具有独特和特征性的不良反应,在日本患者中,这些不良反应的特征尚未被很好地了解,因为大多数临床试验都是在欧洲和美国进行的。相比之下,免疫疗法正在重新被考虑用于选择更合适的患者,或者作为与其他药物联合治疗的形式,因为分子靶向治疗获得的完全缓解较少,且存在意想不到的不良反应。目前我们有几种靶向药物可供选择,将来会有更多的药物,我们将在各种临床环境中实际使用这些药物,如术前、辅助治疗、序贯给药和联合给药,除了细胞因子。因此,我们需要更详细的研究来获得最佳的治疗方法,以最大限度地发挥这些药物的作用,延长转移性肾细胞癌患者的总生存期,同时保持其生活质量。在本文中,我们回顾了与转移性肾细胞癌现有药物治疗相关的问题。

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