Dahl Olav, Fluge Øystein, Carlsen Erik, Wiig Johan N, Myrvold Helge E, Vonen Barthold, Podhorny Nina, Bjerkeset Ottar, Eide Tor Jack, Halvorsen Tore B, Tveit Kjell Magne
Olav Dahl, Section for Oncology, Institute of Medicine, University of Bergen, Norway.
Acta Oncol. 2009;48(3):368-76. doi: 10.1080/02841860902755244.
The recommendation of adjuvant chemotherapy for colon cancer with lymph node metastases, based on two studies from USA, was reluctantly accepted by Norwegian medical doctors. It was therefore decided to assess the role of adjuvant therapy with 5fluorouracil (5-FU) combined with levamisole (Lev) in a confirmatory randomised study.
Four hundred and twenty five patients with operable colon and rectum cancer, Stage II and III (Dukes' stage B and C), were from January 1993 to October 1996, included in a randomised multicentre trial in Norway. The age limits were 18-75 years. Therapy started with a loading course of bolus i.v. 5-FU (450 mg/m(2)) daily for 5 days and p.o. doses of Lev (50 mg x 3) for 3 days. From day 28 a weekly i.v. 5-FU dose (450 mg/m(2)) were administered for 48 weeks. From day 28 also p.o. doses of Lev (50 mg x 3) for 3 days were given every 14 days. In total 214 patients were randomised to 5FU/Lev and 211 were included in the control group with surgery alone. Some did not comply with the inclusion and exclusion criteria, thus leaving 206 evaluable patients in each group.
There was no significant survival difference between the two groups at 5 years: Disease-free survival (DFS) was 73% after chemotherapy, 68% (p=0.24) in the control group, and corresponding cancer specific survival (CSS) 75% and 71%, respectively (p=0.69). There was no difference between the two groups when analysed for colon and rectum separately. However, the subgroup of colon cancer with stage III exhibited a statistically significant difference both for DFS, 58% vs. 37% (p=0.012) and CSS, 65% vs. 47% (p=0.032) in favour of adjuvant chemotherapy. The benefit was further statistically significant for women but not for men. Toxicity was generally mild and acceptable with no drug related fatalities.
Colon cancer patients with lymph node metastases benefit from adjuvant chemotherapy with 5-FU/Lev with acceptable toxicity. In a subgroup analysis females did better than males. Rectal cancer does not benefit from this regimen.
基于美国的两项研究，针对伴有淋巴结转移的结肠癌患者辅助化疗的建议，挪威医生勉强接受。因此决定在一项验证性随机研究中评估5-氟尿嘧啶（5-FU）联合左旋咪唑（Lev）辅助治疗的作用。
1993年1月至1996年10月，425例可手术的结肠癌和直肠癌患者（II期和III期，Dukes分期B和C）纳入挪威一项随机多中心试验。年龄限制为18至75岁。治疗开始时先进行静脉推注5-FU（450mg/m²）每日1次，共5天的负荷疗程，以及口服Lev（50mg×3）共3天。从第28天起，每周静脉注射5-FU剂量（450mg/m²），共48周。从第28天起，每14天也口服Lev（50mg×3）共3天。总共214例患者随机分配至5-FU/Lev组，211例纳入单纯手术对照组。部分患者不符合纳入和排除标准，因此每组留下206例可评估患者。
两组5年生存率无显著差异：化疗后无病生存率（DFS）为73%，对照组为68%（p = 0.24），相应的癌症特异性生存率（CSS）分别为75%和71%（p = 0.69）。分别分析结肠癌和直肠癌时，两组无差异。然而，III期结肠癌亚组在DFS方面显示出统计学显著差异，分别为58%对37%（p = 0.012），CSS为65%对47%（p = 0.032），支持辅助化疗。该益处对女性有统计学显著意义，对男性则无。毒性一般较轻且可接受，无药物相关死亡。
伴有淋巴结转移的结肠癌患者从5-FU/Lev辅助化疗中获益，毒性可接受。亚组分析显示女性效果优于男性。直肠癌未从此方案中获益。
