City of Hope Comprehensive Cancer Center, Department of Medical Oncology & Experimental Therapeutics, 1500 East Duarte Road, Duarte, CA 91010, USA.
Expert Opin Investig Drugs. 2012 Dec;21(12):1851-9. doi: 10.1517/13543784.2012.733695. Epub 2012 Sep 26.
Tivozanib is a novel tyrosine kinase inhibitor (TKI) which inhibits vascular endothelial growth factor (VEGF) receptors-1, -2, and -3 at nanomolar concentrations.
A comprehensive MEDLINE and American Society of Clinical Oncology abstract search was performed to gather all relevant clinical and translational data related to tivozanib. We discuss pre-clinical studies associated with tivozanib, and the results of a Phase I assessment in advanced solid tumors. We highlight combination studies with tivozanib, including pairings of tivozanib with cytotoxic therapy in patients with colorectal cancer and breast cancer. A randomized discontinuation Phase II study and a randomized Phase III study assessing the activity of tivozanib in metastatic renal cell carcinoma (mRCC) are described in detail.
Tivozanib will face the challenge of entering an already crowded therapeutic space in mRCC-emerging combination studies and biomarker assessments may distinguish this agent among other VEGF-TKIs. The current review will outline the development pathway of tivozanib to date, and offer lessons learned and future opportunities.
替沃扎尼布是一种新型的酪氨酸激酶抑制剂(TKI),能以纳摩尔浓度抑制血管内皮生长因子(VEGF)受体-1、-2 和 -3。
对 MEDLINE 和美国临床肿瘤学会摘要进行了全面检索,以收集与替沃扎尼布相关的所有临床和转化研究数据。我们讨论了与替沃扎尼布相关的临床前研究,以及在晚期实体瘤中进行的 I 期评估结果。我们重点介绍了替沃扎尼布的联合研究,包括替沃扎尼布与结直肠癌和乳腺癌患者的细胞毒性治疗联合使用。详细描述了一项评估替沃扎尼布在转移性肾细胞癌(mRCC)中的活性的随机停药 II 期研究和一项随机 III 期研究。
替沃扎尼布将面临在 mRCC 中进入一个已经拥挤的治疗领域的挑战——新兴的联合研究和生物标志物评估可能会使该药物在其他 VEGF-TKI 中脱颖而出。本综述概述了替沃扎尼布迄今为止的开发途径,并提供了经验教训和未来机遇。