Shahani Rohan, Kwan Kevin G, Kapoor Anil
Division of Urology, Department of Surgery, St. Joseph's Healthcare Hamilton and McMaster University, Hamilton, Ontario, Canada.
Drug Healthc Patient Saf. 2010;2:85-91. doi: 10.2147/dhps.s6467. Epub 2010 Jun 28.
Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma.
肾细胞癌（RCC）是最致命的泌尿生殖系统恶性肿瘤之一。最近，晚期RCC的治疗模式发生了转变。包括血管内皮生长因子（VEGF）和雷帕霉素哺乳动物靶点（mTOR）抑制剂在内的新型靶向治疗药物已被研发出来，这些药物在原本治疗选择很少的患者群体中显示出了有前景的结果。首个mTOR抑制剂替西罗莫司是一种静脉注射前体药物，已在预后较差的患者中显示出总体生存期的改善。最近，一种口服mTOR抑制剂依维莫司（RAD 001）已被研发出来，它已被证明可延缓在其他靶向治疗中病情进展的转移性RCC患者的疾病进展。尽管依维莫司在III期试验中显示出了生存优势，但其相关的全身毒性虽然总体耐受性良好，但也不容忽视。这些毒性包括粘膜炎、高血糖、高脂血症和肺炎。尽管有副作用，但新出现的证据表明依维莫司是晚期肾细胞癌患者的最佳二线治疗药物。
