Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France.
Semin Oncol. 2013 Aug;40(4):472-81. doi: 10.1053/j.seminoncol.2013.05.010.
The standard strategy in metastatic renal cell carcinoma (mRCC) is to use sequential treatment. Different pathways are known to be involved in the pathogenesis of mRCC and in the development of resistance to targeted drugs. Combinations of targeted drugs could theoretically achieve better inhibition of a given pathway, inhibition of different pathways, or inhibition of a pathway involved in the resistance to a given drug. However, there is as yet no clear evidence that combination therapy is of clinical benefit and excess toxicity has been observed. In mRCC the majority of studies have explored combinations of vascular endothelial growth factor (VEGF) inhibitors and mammalian target of rapamycin (mTOR) inhibitors. A new generation of VEGF tyrosine kinase inhibitors (TKIs) seems to be more tolerable, and therefore potentially easier to combine with other agents. Trials with PI3K/akt/mTORC1/2 inhibitor combinations and with other new targeted drugs are also ongoing.
转移性肾细胞癌 (mRCC) 的标准治疗策略是采用序贯治疗。已知不同的途径参与 mRCC 的发病机制和靶向药物耐药的发展。靶向药物的联合应用理论上可以更好地抑制特定途径、抑制不同途径或抑制与特定药物耐药相关的途径。然而，目前尚无明确证据表明联合治疗具有临床获益，并且观察到过度毒性。在 mRCC 中，大多数研究都探讨了血管内皮生长因子 (VEGF) 抑制剂和哺乳动物雷帕霉素靶蛋白 (mTOR) 抑制剂的联合应用。新一代 VEGF 酪氨酸激酶抑制剂 (TKI) 似乎更耐受，因此有可能更容易与其他药物联合应用。PI3K/akt/mTORC1/2 抑制剂联合应用和其他新型靶向药物的试验也在进行中。
