Advanced renal cell carcinoma - current and emerging management strategies
Advanced renal cell carcinoma - current and emerging management strategies
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DOI：
10.2165/00003495-200767090-00002
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发表时间：
2007-01-01
期刊：
影响因子：
11.5
通讯作者：
Escudier, Bernard
中科院分区：
文献类型：
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作者：
Escudier, Bernard
近年来，肾细胞癌（RCC）的治疗取得了相当大的进展，并且正在开发新的新兴策略。根据21世纪初两项随机研究的结果，肾切除术现在已成为细胞减灭术的标准，然后才开始用细胞因子进行全身治疗。直到2006年，白细胞介素（IL）-2和干扰素是转移性RCC（MRCC）的标准治疗。这两种药物在MRCC中已经使用了超过20年，但其疗效仍存在争议。根据许多研究，这些药物不应给予预后不良的患者。在具有良好预后因素的患者中，基于阿托伐他汀的方案应作为高剂量IL-2或皮下方案的标准。法国珀西Quattro研究的结果鼓励在中等风险的患者中使用新的靶向治疗作为一线治疗。在RCC中开发靶向治疗是必要的，主要是因为Von Hippel-Lindau（VHL）基因在散发性RCC中经常发生突变。VHL蛋白异常导致缺氧诱导因子（HIF）-α的积累和一系列基因的激活，包括血管内皮生长因子（VEGF），从而诱导血管生成。最近许多阻断VEGF通路的新药研究的结果已被报道，并为MRCC患者提供了新的策略选择。舒尼替尼和索拉非尼是两种酪氨酸激酶抑制剂，与标准治疗相比，可改善RCC患者的无进展生存期，最近已获得批准。替西罗莫司是雷帕霉素抑制剂调节HIF-α的哺乳动物靶点，可改善风险特征较差的RCC患者的生存率。贝伐单抗是一种抗VEGF的单克隆抗体，已显示出非常有前途的疗效。总体而言，MRCC的治疗目前正从细胞因子时代转向靶向药物时代。然而，关于联合治疗的有效性和实现完全缓解的最佳方法仍然存在许多问题，这可能是治愈MRCC的最佳希望。
Management of renal cell carcinoma (RCC) has made considerable progress in recent years, and new emerging strategies are being developed. On the basis of the results of two randomised studies in the early 2000s, nephrectomy has now become the standard as cytoreductive surgery before embarking on systemic treatment with cytokines. Interleukin (IL)-2 and interferon were the standard treatment in metastatic RCC (MRCC) until 2006. The efficacy of these two drugs, which have now been used for >20 years in MRCC, is still controversial. On the basis of many studies, these drugs should not be given to patients with a poor prognosis. In patients with good prognostic factors, a cytokine-based regimen should remain the standard as either a high-dose IL-2 or subcutaneous regimen. In patients with intermediate risk, the results of the French Percy Quattro study encourage the use of new targeted therapies as first-line therapy.Development of targeted therapies in RCC has been necessary largely because the Von Hippel-Lindau (VHL) gene is often mutated in sporadic RCC. VHL protein abnormalities lead to accumulation of hypoxia-inducible factor (HIF)-alpha and activation of a series of genes, including vascular endothelial growth factor (VEGF), thus inducing angiogenesis. Results from many recent studies with new agents that block the VEGF pathway have been reported and offer new strategic options for patients with MRCC. Sunitinib and sorafenib, two tyrosine kinase inhibitors, improve progression-free survival in RCC compared with standard treatment and have been recently approved. Temsirolimus, a mammalian target of rapamycin inhibitor regulating HIF-alpha, improves survival in RCC patients with poor risk features. Bevacizumab, a monoclonal antibody against VEGF, has shown very promising efficacy. Overall, treatment of MRCC is currently moving from the cytokine era to the targeted agent era. However, many questions still remain regarding the efficacy of combination treatments and on the best way to achieve complete remission, which is probably the best hope of curing MRCC.