Davidson Brittany A, Secord Angeles Alvarez
Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Int J Womens Health. 2014 Mar 13;6:289-300. doi: 10.2147/IJWH.S49781. eCollection 2014.
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS) benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3), platelet-derived growth factor (-α and -β), and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit), interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC.
上皮性卵巢癌(EOC)是最致命的妇科癌症。最近,临床试验聚焦于新型抗血管生成药物,这些药物可与化疗联合使用,或单独用于原发性和复发性卵巢癌女性患者。抗血管生成药物包括单克隆抗体、酪氨酸激酶抑制剂和肽抗体。其中许多药物,包括贝伐单抗、帕唑帕尼、尼达尼布、西地尼布和曲贝替定,已在随机III期临床试验中进行了评估,且均显示出无进展生存期(PFS)获益。具体而言,维持使用帕唑帕尼可改善新诊断EOC女性患者的PFS。帕唑帕尼是一种口服酪氨酸激酶抑制剂,可抑制多种激酶受体,包括血管内皮生长因子(-1、-2、-3)、血小板衍生生长因子(-α和-β)和成纤维细胞生长因子的受体。它还靶向干细胞因子受体(c-kit)、白细胞介素2诱导性T细胞激酶、淋巴细胞特异性蛋白酪氨酸激酶和集落刺激因子1受体。帕唑帕尼已在多项II期和III期临床试验中进行了研究,结果表明其在EOC治疗中具有潜在作用。本文概述了帕唑帕尼在EOC治疗中的应用。