Division of Hematology-Oncology, Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA, USA.
Clin Colorectal Cancer. 2012 Mar;11(1):1-13. doi: 10.1016/j.clcc.2011.05.005. Epub 2011 Jul 12.
Over the past 8 to 10 years, significant advances have been made in the treatment of metastatic colorectal cancer (mCRC). In particular, the development of the targeted biologic agents bevacizumab, cetuximab, and panitumumab, and their integration with cytotoxic chemotherapy regimens has led to improvements in clinical efficacy. Despite these gains, the overall impact of current targeted agents in the treatment of mCRC has been relatively modest, and while 2-year survival has improved, no gains have been made, as of yet, in 5-year survival. Intense efforts continue to be focused on developing novel targeted agents with a different spectrum of activity. Presently, five novel targeted molecules are in phase III trials, including the antiangiogenesis agents aflibercept and ramucirumab, two novel receptor tyrosine kinase inhibitors, regorafenib and brivanib, and the Akt inhibitor perifosine. There are an additional 52 phase II trials investigating a wide range of other candidate molecules. The potential list of approved targeted agents in mCRC seems likely to increase over the next 5 to 10 years. To maximize their potential clinical impact, however, it will be critically important to introduce efficient molecular diagnostic methodologies into the drug development process for the identification and validation of predictive biomarkers for chemosensitivity. This article reviews the development of targeted agents for the treatment of mCRC, including the three molecules currently approved by the US Food and Drug Administration (FDA), as well as the main non-FDA-approved therapeutics currently undergoing phase II and III clinical testing.
在过去的 8 到 10 年中，转移性结直肠癌（mCRC）的治疗取得了重大进展。特别是靶向生物制剂贝伐珠单抗、西妥昔单抗和帕尼单抗的发展，以及它们与细胞毒性化疗方案的整合，导致了临床疗效的提高。尽管取得了这些进展，但目前靶向药物在 mCRC 治疗中的总体影响相对较小，尽管 2 年生存率有所提高，但 5 年生存率尚未提高。目前，仍在集中精力开发具有不同作用谱的新型靶向药物。目前，有五种新型靶向分子正在进行 III 期临床试验，包括抗血管生成药物阿柏西普和雷莫芦单抗、两种新型受体酪氨酸激酶抑制剂regorafenib 和 brivanib 以及 Akt 抑制剂 perifosine。还有另外 52 项 II 期试验正在研究广泛的其他候选分子。在未来 5 到 10 年内，mCRC 中获得批准的靶向药物的潜在清单似乎可能会增加。然而，为了最大限度地发挥其潜在的临床影响，将高效的分子诊断方法引入药物开发过程，以确定和验证化疗敏感性的预测生物标志物将是至关重要的。本文回顾了用于治疗 mCRC 的靶向药物的开发，包括目前获得美国食品和药物管理局（FDA）批准的三种药物，以及目前正在进行 II 期和 III 期临床试验的主要非 FDA 批准的治疗药物。
