Leyland-Jones B, Burdette-Radoux S
Department of Oncology, McGill University, Montreal, Quebec, Canada.
J Gastrointest Surg. 1997 Nov-Dec;1(6):576-82. doi: 10.1016/s1091-255x(97)80075-3.
The current phase III studies of chemotherapy in advanced colorectal cancer include 60% to 85% of patients with the liver as a site of metastatic disease. Within the past 10 years, various modulatory combinations of 5-fluorouracil (5-FU) with agents such as leucovorin, interferon, N-(phosphonacetyl)-L-aspartate (PALA), and methotrexate have produced higher response rates than 5-FU alone. A major seven-arm study, conducted by the Southwestern Oncology Group and reported in 1995, suggested that single-agent, continuous-infusion 5-FU demonstrated the most encouraging results. Nine of 12 reported randomized studies comparing the combination of 5-FU and leucovorin with 5-FU alone report significant increases in response rates; two studies reported significant increases in survival. The meta-analysis project involving 1381 patients confirmed the increase in response rate with the combination (23%) vs. 5-FU alone (11%) but did not demonstrate any significant difference in median survival. The current issues involving 5-FU administration largely concentrate on the best approach (modulation vs. scheduling) and comprehensive evaluation of end points (quality of life, survival, and pharmacoeconomics). The current literature examining quality-of-life issues suggests that 5-FU and low-dose leucovorin produce the best overall improvement in symptoms. Others argue that continuous-infusion scheduling is also associated with a very good quality of life (although the increased cost and morbidity of continuous-infusion administration has to be factored into this consideration). An important phase III study is currently being conducted by the National Cancer Institute of Canada comparing immediate vs. delayed (until symptomatic) chemotherapy in patients with advanced colorectal cancer. Of the new approaches to therapy, perhaps the most immediately applicable are the new thymidylate synthase inhibitors (in particular, Tomudex, which produces a response rate equivalent to that of 5-FU plus leucovorin with less toxicity and a more convenient schedule).
目前针对晚期结直肠癌的化疗III期研究中，60%至85%的患者存在肝脏转移病灶。在过去10年里，5-氟尿嘧啶（5-FU）与亚叶酸、干扰素、N-(膦酰乙酰)-L-天冬氨酸（PALA）和甲氨蝶呤等药物的各种调节性联合用药方案，产生的缓解率高于单独使用5-FU。西南肿瘤协作组于1995年开展并报告的一项大型七臂研究表明，单药持续输注5-FU显示出最令人鼓舞的结果。在12项报告的随机研究中，有9项比较了5-FU与亚叶酸联合用药和单独使用5-FU的情况，结果显示联合用药组的缓解率显著提高；有2项研究报告联合用药组的生存率显著提高。一项涉及1381名患者的荟萃分析项目证实，联合用药组的缓解率有所提高（23%），而单独使用5-FU组为（11%），但在中位生存期方面未显示出任何显著差异。目前与5-FU给药相关的问题主要集中在最佳方法（调节与给药方案）以及终点指标的综合评估（生活质量、生存率和药物经济学）。目前有关生活质量问题的文献表明，5-FU与低剂量亚叶酸联合使用能在症状改善方面产生最佳的总体效果。其他人则认为持续输注给药方案也与良好的生活质量相关（尽管持续输注给药增加的成本和发病率也必须纳入这一考量）。加拿大国家癌症研究所目前正在进行一项重要的III期研究，比较晚期结直肠癌患者立即化疗与延迟化疗（直至出现症状）的效果。在新的治疗方法中，或许最直接适用的是新型胸苷酸合成酶抑制剂（特别是Tomudex，其产生的缓解率与5-FU加亚叶酸相当，但毒性更低且给药方案更方便）。
