O'Neil Bert H, Goldberg Richard M
University of North Carolina, Division of Hematology and Oncology, Chapel Hill, NC 27599-7305, USA.
Expert Opin Investig Drugs. 2003 Dec;12(12):1939-49.
Colorectal cancer is a common disease with a high rate of mortality and very well-understood genetics. Primary therapy still consists of relatively non-specific treatments: surgery, radiotherapy and chemotherapy. In this article, recent data in the now fast-moving field of treatment of unresectable metastatic colorectal cancer are reviewed, beginning with new developments in conventional cytotoxic therapies. A number of new cytotoxic agents appear to have at least some activity in this disease, including classes of drugs that have been effective to date. The very rapidly growing area of targeted therapy will also be expanded upon. This year, for the first time, there has been a targeted therapy shown convincingly to prolong survival for patients with unresectable metastatic colorectal cancer in a well-performed Phase III trial. This agent is bevacizumab, a humanised monoclonal antibody targeting the circulating proangiogenic growth factor vascular endothelial growth factor. Results with bevacizumab should lead to rapid expansion of the number of strategies targeting tumour neovasculature. Additionally, an antibody against the epidermal growth factor, cetuximab, has been shown to have both single-agent activity and the potential ability to partially reverse resistance to a chemotherapy drug. These advancements, as well as data on other novel treatment agents that have been studied specifically in patients with colorectal neoplasms, are discussed in detail.
结直肠癌是一种常见疾病，死亡率高，其遗传学特征也为人熟知。主要治疗方法仍然包括相对非特异性的治疗手段：手术、放疗和化疗。本文回顾了目前进展迅速的不可切除转移性结直肠癌治疗领域的最新数据，首先介绍传统细胞毒性疗法的新进展。一些新型细胞毒性药物似乎对这种疾病至少有一定活性，包括迄今已证实有效的几类药物。靶向治疗这一快速发展的领域也将得到进一步阐述。今年，在一项精心设计的III期试验中，首次有靶向治疗被令人信服地证明可延长不可切除转移性结直肠癌患者的生存期。这种药物是贝伐单抗，一种靶向循环促血管生成生长因子血管内皮生长因子的人源化单克隆抗体。贝伐单抗的研究结果应会促使针对肿瘤新生血管的治疗策略迅速增加。此外，一种抗表皮生长因子的抗体西妥昔单抗已显示出单药活性以及部分逆转对一种化疗药物耐药性的潜在能力。本文将详细讨论这些进展以及专门针对结直肠肿瘤患者研究的其他新型治疗药物的数据。
