Carmichael Courtney, Lau Clayton, Josephson David Y, Pal Sumanta K
City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Clin Adv Hematol Oncol. 2012 May;10(5):307-14.
The landscape of treatment for metastatic renal cell carcinoma (mRCC) continues to evolve. Although several new drugs have been approved for the treatment of this disease in recent years, mRCC remains incurable. Thus, the search continues for new effective therapies. One such novel compound is axitinib (Inlyta, Pfizer), a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. Following phase I testing in advanced solid tumors (where hypertension, stomatitis, and diarrhea were the dose-limiting toxicities), use of axitinib has been further developed through phase II testing in thyroid, breast, lung, and renal cancers. Recently, the phase III AXIS (Axitinib [AG 013736] as Second Line Therapy for Metastatic Renal Cell Cancer) trial demonstrated an improvement in progression-free survival for patients with mRCC who were treated with axitinib versus sorafenib (Nexavar, Bayer) as second-line therapy. This article describes the preclinical and clinical evolution of axitinib, with an emphasis on its development and role in mRCC.
转移性肾细胞癌（mRCC）的治疗格局在持续演变。尽管近年来有几种新药被批准用于治疗这种疾病，但mRCC仍然无法治愈。因此，对新的有效疗法的探索仍在继续。一种这样的新型化合物是阿昔替尼（英利达，辉瑞公司），一种强效的血管内皮生长因子受体酪氨酸激酶抑制剂。在晚期实体瘤中进行I期试验（其中高血压、口腔炎和腹泻是剂量限制性毒性）后，阿昔替尼已通过在甲状腺癌、乳腺癌、肺癌和肾癌中的II期试验得到进一步开发。最近，III期AXIS（阿昔替尼[AG 013736]作为转移性肾细胞癌的二线治疗）试验表明，接受阿昔替尼治疗的mRCC患者与接受索拉非尼（多吉美，拜耳公司）作为二线治疗的患者相比，无进展生存期有所改善。本文描述了阿昔替尼的临床前和临床演变，重点是其在mRCC中的开发和作用。
