Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa FL, USA.
Ther Adv Urol. 2013 Oct;5(5):223-32. doi: 10.1177/1756287213495099.
The landscape of treatment for advanced/metastatic renal cell carcinoma (mRCC) has advanced significantly in the last decade and continues to evolve with the approval of new drugs targeting the vascular endothelial growth factor (VEGF) and its receptors and mammalian target of rapamycin (mTOR). Currently available oral VEGF tyrosine kinase inhibitors (TKIs) approved for treatment of mRCC include sorafenib, sunitinib, pazopanib, and axitinib. This review focuses on pazopanib, a multikinase VEGF TKI indicated for patients with treatment-naïve and cytokine-refractory mRCC. This article describes the preclinical and clinical evolution of pazopanib, with an emphasis on its development and role in mRCC. Pivotal trials are discussed that demonstrate the efficacy and safety of pazopanib and its important role in the treatment of patients with mRCC in comparison to other available treatment options. The clinical path of pazopanib continues to develop further, with several ongoing studies exploring its role in neoadjuvant and adjuvant RCC. Furthermore, its potential role in sequential and combination studies with other VEGFR and non-VEGFR targeted agents is discussed. Overall, pazopanib is a unique VEGF TKI, with a different and more favorable safety profile compared with other members of the VEGF TKI family and represents an attractive alternative for patients with mRCC.
过去十年中,晚期/转移性肾细胞癌(mRCC)的治疗格局取得了重大进展,随着针对血管内皮生长因子(VEGF)及其受体和哺乳动物雷帕霉素靶蛋白(mTOR)的新药的批准,这一进展仍在继续。目前可用于治疗 mRCC 的口服 VEGF 酪氨酸激酶抑制剂(TKI)包括索拉非尼、舒尼替尼、帕唑帕尼和阿昔替尼。本文重点介绍帕唑帕尼,一种用于治疗初治和细胞因子难治性 mRCC 的多激酶 VEGF TKI。本文描述了帕唑帕尼的临床前和临床演变,重点介绍了其在 mRCC 中的开发和作用。讨论了关键性试验,这些试验证明了帕唑帕尼的疗效和安全性,以及与其他可用治疗方案相比,它在 mRCC 患者治疗中的重要作用。帕唑帕尼的临床路径继续进一步发展,多项正在进行的研究探讨了其在新辅助和辅助肾细胞癌中的作用。此外,还讨论了其在与其他 VEGFR 和非 VEGFR 靶向药物的序贯和联合研究中的潜在作用。总体而言,帕唑帕尼是一种独特的 VEGF TKI,与 VEGF TKI 家族的其他成员相比,具有不同且更有利的安全性特征,是 mRCC 患者的一种有吸引力的选择。