Jackson Amanda L, Eisenhauer Eric L, Herzog Thomas J
University of Cincinnati Medical Center, Division of Gynecologic Oncology , 222 Piedmont Ave, Suite 4100, Cincinnati, OH 45219 , USA.
Expert Opin Emerg Drugs. 2015 Jun;20(2):331-46. doi: 10.1517/14728214.2015.1036739.
Patients with epithelial ovarian cancer (EOC) have a high rate of recurrence, and overall survival remains at ∼ 25%. There is a need for new treatments that can increase progression free survival and quality of life. Recent clinical trials focus on angiogenesis, VEGFs, and tyrosine kinase inhibitors that play a role in recurrence, metastasis, and ascites in EOC.
This review summarizes clinical rationale, mechanisms of action, and clinical data for angiogenesis inhibitors under evaluation in Phase II and III trials for EOC. Anti-angiogenesis agents reviewed in this paper include aflibercept, bevacizumab, cediranib, fosbretabulin, imatinib, nintedanib, pazopanib, saracatinib, sorafenib, sunitinib, and trebananib.
These agents have particular rationale for potential use in EOC due to the molecular changes associated with EOC tumorigenesis, namely a significant increase in angiogenic activity. Due to the costs and toxicities associated with anti-angiogenics, biomarker or molecular signature selection strategy for patients who will most benefit would be ideal but no such strategy has been validated to date.
上皮性卵巢癌(EOC)患者复发率高,总体生存率仍约为25%。需要新的治疗方法来提高无进展生存期和生活质量。近期的临床试验聚焦于血管生成、血管内皮生长因子(VEGFs)以及在EOC复发、转移和腹水形成中起作用的酪氨酸激酶抑制剂。
本综述总结了正在EOC的II期和III期试验中评估的血管生成抑制剂的临床原理、作用机制和临床数据。本文所综述的抗血管生成药物包括阿柏西普、贝伐单抗、西地尼布、磷丙泊酚二钠、伊马替尼、尼达尼布、帕唑帕尼、萨拉替尼、索拉非尼、舒尼替尼和曲贝替定。
由于与EOC肿瘤发生相关的分子变化,即血管生成活性显著增加,这些药物在EOC中具有潜在应用的特殊原理。鉴于抗血管生成药物的成本和毒性,为最有可能受益患者选择生物标志物或分子特征的策略将是理想的,但迄今为止尚无此类策略得到验证。