Billemont Bertrand, Méric Jean-Baptiste, Izzedine Hassan, Taillade Laurent, Sultan-Amar Valentine, Rixe Olivier
Hôpital Pitié-Salpêtrière, Service d'oncologie médicale, 47, boulevard de l'Hôpital, 75013 Paris.
Bull Cancer. 2007 Jul;94 Spec No:S232-40.
Developments in the knowledge of molecular biology of renal cell carcinoma (RCC) over the past 20 years have been identified. Angiogenesis is playing a key role in the physiopathology of RCC. Von Hippel-Lindau (VHL) alterations, HIFalpha accumulation and vascular endothelial growth factor (VEGF) overexpression are important mediators of this process. Several stategies have been developped to target angiogenesis for the treatment of metastatic RCC. These include inhibition of VEGF receptors (inhibition of the tyrosine kinase activity) or binding to the VEGF protein. Several additional kinases inhibitions including PDGF receptors are also targeted. Sunitinib (SU11248) is an orally biovailable small molecule that has demonstrated superiority over interferon-alpha for the treatment of metastatic RCC. In a recent randomized phase III study conducted in 750 patients, the response rate to sunitinib was 31% and to interferon 6%. The median of progression free survival (PFS) was 11 months for sunitinib and 5 months for interferon (p < 0.001). Sorafenib (BAY43-9006) was found to inhibit Raf1, but also VEGFR2 and 3, Flt3, PDGFR-a and b and c-kit, has been tested in a phase III study against placebo after one prior systemic therapy. The median of the time to progression (TTP) for sorafenib was 24 weeks versus 12 weeks for patients in the placebo arm (p = 0,01). Other molecules tested in metastatic RCC will be presented including axitinib, pazopanib and bevacizumab.
过去20年里，肾细胞癌（RCC）分子生物学知识取得了诸多进展。血管生成在RCC的生理病理学中起着关键作用。冯·希佩尔-林道（VHL）改变、缺氧诱导因子α（HIFα）蓄积以及血管内皮生长因子（VEGF）过表达是这一过程的重要介导因素。已开发出多种针对血管生成来治疗转移性RCC的策略。这些策略包括抑制VEGF受体（抑制酪氨酸激酶活性）或与VEGF蛋白结合。还靶向了包括血小板衍生生长因子（PDGF）受体在内的其他几种激酶抑制作用。舒尼替尼（SU11248）是一种口服生物可利用的小分子，已证明其在治疗转移性RCC方面优于α干扰素。在最近一项纳入750例患者的随机III期研究中，舒尼替尼的缓解率为31%，干扰素为6%。舒尼替尼的无进展生存期（PFS）中位数为11个月，干扰素为5个月（p<0.001）。索拉非尼（BAY43 - 9006）被发现可抑制Raf1，还可抑制VEGFR2和3、Flt3、PDGFR - a和b以及c - kit，在一项针对接受过一次全身治疗后的患者与安慰剂对照的III期研究中进行了测试。索拉非尼的疾病进展时间（TTP）中位数为24周，而安慰剂组患者为12周（p = 0.01）。还将介绍在转移性RCC中测试的其他分子，包括阿昔替尼、帕唑帕尼和贝伐单抗。
