Complexo Hospitalario Arquitecto Marcide, Ferrol, Spain.
Clin Transl Oncol. 2013 Jun;15(6):425-33. doi: 10.1007/s12094-012-0985-x. Epub 2013 Feb 12.
We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC.
我们进行了一项文献检索，研究了索拉非尼作为一线或二线治疗药物的作用机制涉及的信号通路，并考虑了其毒性特征。与同一适应证的其他药物相比，索拉非尼的耐受性似乎更好。即使在先前的血管内皮生长因子受体抑制剂治疗失败后，酪氨酸激酶抑制剂（TKI）之间也可能存在有限的交叉耐药性，但 TKI 的最佳应用顺序仍有待确定。二线治疗方案的随机试验在无进展生存期（PFS）和总生存期（OS）方面显示出适度或无差异。索拉非尼和阿昔替尼的直接比较显示，在 PFS 方面，阿昔替尼更有优势，但在 OS 方面作为二线治疗并无优势。相比之下，一项 III 期研究显示，与替西罗莫司相比，索拉非尼在 OS 方面具有获益。总之，在使用其他 VEGF 抑制剂（如舒尼替尼）后，索拉非尼作为治疗晚期或转移性肾细胞癌的药物仍然具有活性和安全性。
