Miyamoto Shingo, Kakutani Shigenori, Sato Yujiro, Hanashi Akira, Kinoshita Yoshitaka, Ishikawa Akira
Department of Medical Oncology.
Department of Urology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.
Jpn J Clin Oncol. 2018 Jun 1;48(6):503-513. doi: 10.1093/jjco/hyy053.
Pazopanib (Votrient®) is an oral small-molecule multi-kinase inhibitor that primarily inhibits vascular endothelial growth factor receptor-1, -2 and -3, platelet endothelial growth factor receptor-α, and -β, and the stem-cell factor receptor c-kit. In preliminary experiments using angiogenesis models with mice and rabbits, pazopanib inhibited angiogenesis caused by combined vascular endothelial growth factor and basic fibroblast growth factor. Although pazopanib was developed as a therapeutic agent against various tumors, it is currently approved in many countries for advanced soft-tissue sarcoma and renal cell carcinoma. The importance of pazopanib has been acknowledged, with positive results demonstrated in large-scale clinical trials involving patients with soft-tissue sarcoma and renal cell carcinoma. However, adverse events such as liver dysfunction and hypertension are common, often necessitating treatment discontinuation. These adverse events are generally manageable, and from the perspective of health-related quality of life and cost-effectiveness, pazopanib provides an improvement in quality-adjusted life years and decreases the treatment cost compared with other alternatives. In this review, we present the results of clinical trials and discuss the pharmacological action of pazopanib, with the aim of evaluating its current state by examining various associated issues.
帕唑帕尼（Votrient®）是一种口服小分子多激酶抑制剂，主要抑制血管内皮生长因子受体-1、-2和-3、血小板内皮生长因子受体-α和-β，以及干细胞因子受体c-kit。在使用小鼠和兔子血管生成模型的初步实验中，帕唑帕尼抑制了由血管内皮生长因子和碱性成纤维细胞生长因子联合引起的血管生成。尽管帕唑帕尼最初是作为一种针对各种肿瘤的治疗药物开发的，但目前在许多国家被批准用于治疗晚期软组织肉瘤和肾细胞癌。帕唑帕尼的重要性已得到认可，在涉及软组织肉瘤和肾细胞癌患者的大规模临床试验中取得了积极成果。然而，肝功能障碍和高血压等不良事件很常见，常常需要停药。这些不良事件通常是可控的，从健康相关生活质量和成本效益的角度来看，与其他替代药物相比，帕唑帕尼可改善质量调整生命年并降低治疗成本。在本综述中，我们展示了临床试验结果并讨论了帕唑帕尼的药理作用，旨在通过研究各种相关问题来评估其当前状况。
