Punt C J
Department of Medical Oncology, University Hospital Nijmegen, The Netherlands.
Cancer. 1998 Aug 15;83(4):679-89. doi: 10.1002/(sici)1097-0142(19980815)83:4<679::aid-cncr8>3.0.co;2-f.
Treatment with 5-fluorouracil (5-FU) plus leucovorin has been the unofficial standard therapy for patients with colorectal carcinoma (CRC) for more than a decade; however, the optimal dose and schedule remain a matter of debate. Recently several new drugs have shown activity in this disease. These include irinotecan (CPT-11); oxaliplatin; the thymidylate synthase inhibitors raltitrexed, uracil/tegafur (UFT), capecitabine, and S-1; the biochemical modulators trimetrexate and 5-ethynyluracil; and the monoclonal antibody 17-1A.
The results of clinical trials with these and other new agents, as well as their current status and main characteristics, were reviewed.
Several of these agents, some with a novel mechanism of action, show promising activity in CRC. In combination with 5-FU and leucovorin, trimetrexate showed encouraging response rates in Phase II studies. Other interesting agents include capecitabine, UFT, and S-1. The biochemical modulator 5-ethynyluracil may allow the oral administration of 5-FU; however, results of Phase II clinical trials are not yet available. CPT-11 is in the most advanced stage of development and, based on consistent data generated in extensive Phase II studies, currently appears to be a reasonable choice for 5-FU-resistant or refractory disease. Another promising agent is oxaliplatin, which showed activity as first-line and second-line treatment.
Several new agents have shown promise in the treatment of CRC, and changes in the standard treatment of advanced or high risk CRC appear likely in the near future.
十多年来，5-氟尿嘧啶（5-FU）联合亚叶酸一直是结直肠癌（CRC）患者的非官方标准治疗方案；然而，最佳剂量和给药方案仍存在争议。最近，几种新药在该疾病中显示出活性。这些药物包括伊立替康（CPT-11）、奥沙利铂、胸苷酸合成酶抑制剂雷替曲塞、替加氟/尿嘧啶（UFT）、卡培他滨和S-1、生化调节剂三甲曲沙和5-乙炔基尿嘧啶以及单克隆抗体17-1A。
回顾了这些药物及其他新药的临床试验结果、当前状况和主要特征。
其中几种药物，有些具有新颖的作用机制，在结直肠癌中显示出有前景的活性。在II期研究中，三甲曲沙与5-FU和亚叶酸联合使用时显示出令人鼓舞的缓解率。其他有意义的药物包括卡培他滨、UFT和S-1。生化调节剂5-乙炔基尿嘧啶可能使5-FU能够口服给药；然而，II期临床试验的结果尚未可得。CPT-11处于研发的最 advanced 阶段，基于广泛的II期研究中产生的一致数据，目前似乎是5-FU耐药或难治性疾病的合理选择。另一种有前景的药物是奥沙利铂，它作为一线和二线治疗均显示出活性。
几种新药在结直肠癌治疗中显示出前景，晚期或高危结直肠癌的标准治疗在不久的将来可能会发生变化。
