Pouessel D, Patard J-J, Culine S
Hôpital Henri-Mondor, Service d'oncologie médicale, 94010 Créteil cedex, France.
Bull Cancer. 2010;97:83-90. doi: 10.1684/bdc.2010.1073.
Advanced or metastatic renal carcinoma represents a frequent disease in oncologic practice. Few years ago, in immunotherapy era, treatments had quickly reached deadlock. New therapies targeting vascular endothelial growth factors and their receptors (VEGF-R), sorafenib, sunitinib and bevacizumab, and the mammalian target of rapamycin (mTOR), temsirolimus and everolimus, have modified these patients prognosis and their quality of life in a few years. Nevertheless, patients included in randomized trials presented severe inclusion criteria. Then in the daily practice, patients have distinctive characteristics which were not evaluated in large pivotal studies: poor performance status, older patients, renal dysfunction, cerebral metastases or non clear cell renal cancer. In published trials, a few data concerning these situations are reported, and these studies have often included small samples, were retrospective or not randomised. However compared to global population, tolerance have not been very different in geriatric patients, or patients with poor performance status, or with central neurological metastases, or with papillary and chromophobe sub-types. On the contrary progression free or overall survivals increases are more difficult to confirm. Also before starting treatment, ratio between potential benefit and possible toxicities have to be evaluated. In patients with renal insufficiency, VEGF receptor inhibitors seem to be cautiously initiated at reduced doses, and to be increased according to tolerance. Due to these poor proof levels, clinical trials are needed for these specific populations.
晚期或转移性肾癌是肿瘤学实践中常见的疾病。几年前,在免疫治疗时代,治疗很快陷入僵局。靶向血管内皮生长因子及其受体(VEGF-R)的新疗法,索拉非尼、舒尼替尼和贝伐单抗,以及哺乳动物雷帕霉素靶蛋白(mTOR),替西罗莫司和依维莫司,在几年内改变了这些患者的预后和生活质量。然而,纳入随机试验的患者有严格的纳入标准。在日常实践中,患者具有独特的特征,而这些特征在大型关键研究中并未得到评估:体能状态差、老年患者、肾功能不全、脑转移或非透明细胞肾癌。在已发表的试验中,关于这些情况的报道数据较少,而且这些研究通常样本量小,是回顾性的或非随机的。然而,与总体人群相比,老年患者、体能状态差的患者、有中枢神经转移的患者或乳头状和嫌色细胞亚型患者的耐受性并没有太大差异。相反,无进展生存期或总生存期的增加更难得到证实。此外,在开始治疗前,必须评估潜在获益与可能毒性之间的比例。对于肾功能不全的患者,VEGF受体抑制剂似乎应谨慎地以较低剂量开始使用,并根据耐受性增加剂量。由于这些证据水平不足,这些特定人群需要进行临床试验。