University of Genoa, San Martino Hospital and National Institute for Cancer Research, Department of Obstetrics and Gynecology, Largo R. Benzi 1, 16132 Genoa, Italy.
Expert Opin Investig Drugs. 2013 Aug;22(8):1049-62. doi: 10.1517/13543784.2013.802769. Epub 2013 May 15.
Sorafenib is an unselective inhibitor of multiple kinases which has demonstrated clinical advantage in renal cancer and hepatocellular carcinoma. It inhibits tumor proliferation by targeting receptor accessory factor (Raf) kinase isoforms, inhibiting receptor tyrosine kinases of a variety of pro-angiogenic factors and of several receptor tyrosine kinases involved in neovascularization and tumor development.
This review offers an explanation of the mechanism of action and of the pharmacokinetics of sorafenib, and gives readers a complete overview of Phase I and II studies on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment.
The available results from the studies which investigated the use of sorafenib for OC treatment demonstrated poor clinical benefit either as single agent or in combination therapy. The most promising results have been achieved combining sorafenib with bevacizumab, although overlapping and cumulative toxicities should be taken in consideration. Research should focus its attention to the development of reliable predictive biomarkers to assess response and direct therapy in order to allow patient selection and improving treatment schedules maximizing the clinical benefit and simultaneously minimizing the toxicity related to the chemotherapy. Further studies are needed to evaluate the role of sorafenib in the primary treatment of OC.
索拉非尼是一种多激酶的非选择性抑制剂，在肾癌和肝细胞癌中已显示出临床优势。它通过靶向受体辅助因子（Raf）激酶同工型来抑制肿瘤增殖，抑制多种促血管生成因子的受体酪氨酸激酶和几种参与血管生成和肿瘤发展的受体酪氨酸激酶。
本文对索拉非尼的作用机制和药代动力学进行了解释，并全面介绍了索拉非尼在卵巢癌（OC）治疗中的临床疗效、耐受性和安全性的 I 期和 II 期研究结果。
研究表明，索拉非尼作为单一药物或联合治疗OC 的疗效不佳。与贝伐单抗联合应用的结果最有希望，但应考虑重叠和累积毒性。研究应将注意力集中在开发可靠的预测生物标志物上，以评估反应并指导治疗，从而允许患者选择和改进治疗方案，最大限度地提高临床获益，同时最大限度地减少与化疗相关的毒性。需要进一步研究索拉非尼在 OC 初始治疗中的作用。
