Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, UK.
Expert Rev Anticancer Ther. 2013 Jun;13(6):649-60. doi: 10.1586/era.13.40.
Tyrosine kinase inhibitors have revolutionized the treatment of metastatic renal cell carcinoma (RCC). Drugs such as sorafenib, sunitinib and pazopanib act on the VEGF receptor pathway, but they can also inhibit other kinases, resulting in off-target toxicities. Tivozanib was developed due to its potency and selectivity against VEGF receptors 1-3. It has a favorable pharmacokinetic profile after oral administration and a long plasma half-life. In the Phase III TIVO-1 trial, it demonstrated a higher response rate and longer progression-free survival than sorafenib with a better side-effect profile. It is currently awaiting approval to be used in the first-line treatment of metastatic RCC. An early-phase trial has also shown its tolerability at full dose when given with the mTOR inhibitor temsirolimus, suggesting its potential in combination treatment. This article examines tivozanib from its laboratory to clinical development, as well as its relevance and future role in the treatment of RCC in the era of the tyrosine kinase inhibitors.
酪氨酸激酶抑制剂已经彻底改变了转移性肾细胞癌（RCC）的治疗方法。索拉非尼、舒尼替尼和帕唑帕尼等药物作用于 VEGF 受体途径，但也可以抑制其他激酶，导致脱靶毒性。替沃扎尼是由于其对 VEGF 受体 1-3 的效力和选择性而开发的。它在口服后具有良好的药代动力学特征和较长的血浆半衰期。在 III 期 TIVO-1 试验中，它显示出比索拉非尼更高的反应率和更长的无进展生存期，且具有更好的副作用特征。它目前正在等待批准用于转移性 RCC 的一线治疗。一项早期阶段的试验还表明，当与 mTOR 抑制剂替西罗莫司联合使用时，替沃扎尼在全剂量下具有耐受性，这表明其在联合治疗中的潜力。本文从实验室到临床开发检查了替沃扎尼，以及它在酪氨酸激酶抑制剂时代 RCC 治疗中的相关性和未来作用。
