*Renal Cancer Unit, Department of Medicine, Royal Marsden, London, UK †H. Lee Moffitt Cancer Center, Tampa, FL ‡Cleveland Clinic Cancer Institute, Cleveland, OH §Massachusetts General Hospital, Boston, MA ∥N.N. Blokhin Russian Cancer Research Center, Moscow, Russia ¶M.D. Anderson Cancer Center, Houston #Texas Oncology PA Sammons Cancer Center/Baylor, Dallas, TX **Department of Urology, University of Munich, Munich, Germany.
Am J Clin Oncol. 2014 Aug;37(4):397-403. doi: 10.1097/COC.0b013e31827b45f9.
Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.
阿昔替尼是一种新型、口服、多靶点酪氨酸激酶抑制剂，在体外以亚纳摩尔浓度抑制血管内皮生长因子受体 1、2 和 3。在转移性肾细胞癌患者的 III 期临床试验中，阿昔替尼显示出高客观缓解率，并与索拉非尼相比显著延长了无进展生存期。因此，它是第一个在 III 期前瞻性随机试验中证明了酪氨酸激酶抑制剂序贯治疗概念的药物。虽然一般耐受性良好，且毒性 3 级或 4 级的发生率较低，但阿昔替尼表现出独特的不良事件模式，需要监测和管理。阿昔替尼最常见的不良反应包括腹泻、高血压、疲劳、恶心和呕吐。本文总结了观察到的最重要的不良事件，并提出了监测、预防和治疗的建议。这些建议基于现有的文献和 2011 年 7 月在英国伦敦聚集的专门从事转移性肾细胞癌肿瘤治疗的国际医生和护士专家组的讨论。在阿昔替尼治疗期间积极评估和管理不良事件可以最大限度地减少治疗中断并确保治疗的最佳效果。
