Bokemeyer C, Hartmann J T, Kanz L
Eberhard-Karls-Universität, Abteilung Innere Medizin II, Hämatologie und Onkologie, Tübingen.
Praxis (Bern 1994). 1997 Sep 24;86(39):1510-6.
With an annual incidence rate of 30 to 40 per 100,000 colorectal carcinoma is the second most frequent malignancy in Germany. Despite the poor outcome of patients suffering from this disease important advances have been made in the standardisation and improvement of palliative and adjuvant treatment in patients with colorectal cancer. For the systemic chemotherapy 5-fluorouracil (5-FU) remains the most important cytotoxic agent and biomodulation of the therapeutic activity of 5-FU with methotrexate or particularly folinic acid has been clinically established, yielding response rates in 20 to 35% of patients. Current investigations of systemic treatment are aiming into three directions: 1. investigation of high-dose continuous (24-hours) 5-FU application (with or without modulation by folinic acid); 2. evaluation of new, effective cytotoxic agents, among which the camphotecin derivative CPT-11 (irenotecan) and the specific thymidilate synthase inhibitor Tomudex appear to be the most promising drugs as single agents and/or in combination with 5-FU; 3. use of orally available fluoropyrimidine derivatives with high bioavailability which may substantially improve the quality of life in palliative therapy. The postoperative adjuvant treatment of patients with Dukes C colorectal cancer is established clinical practice and the combination of 5-FU and levamisol given for one year will result in an improved overall survival of about 15% at five years compared to surgery alone. Although this regimen remains the current standard treatment, alternatives for the adjuvant treatment may be the use of 5-FU and folinic acid given for only half a year post surgery, locoregional perfusion of the liver with 5-FU alone via the portal vene by 7-day continuous application or the use of 17-1A monoclonal antibody immunotherapy after curative resection. Further improvement may be achieved by the combination of immunotherapy and chemotherapy which is currently tested in clinical studies. Future recommendations for the adjuvant treatment of colorectal cancer will not only be based on therapeutic efficacy but will also have to take costs of treatment into account. Better definition of high-risk patient groups for adjuvant treatment is needed.
在德国,结直肠癌的年发病率为每10万人中有30至40例,是第二常见的恶性肿瘤。尽管患有这种疾病的患者预后较差,但在结直肠癌患者的姑息治疗和辅助治疗的标准化及改善方面已取得了重要进展。对于全身化疗,5-氟尿嘧啶(5-FU)仍然是最重要的细胞毒性药物,5-FU与甲氨蝶呤或特别是亚叶酸的治疗活性生物调节已在临床上确立,20%至35%的患者有反应率。目前全身治疗的研究主要朝着三个方向进行:1. 研究高剂量持续(24小时)应用5-FU(有无亚叶酸调节);2. 评估新的、有效的细胞毒性药物,其中喜树碱衍生物CPT-11(伊立替康)和特异性胸苷酸合成酶抑制剂Tomudex似乎是最有前途的单一药物和/或与5-FU联合使用的药物;3. 使用具有高生物利用度的口服氟嘧啶衍生物,这可能会显著改善姑息治疗中的生活质量。对Dukes C期结直肠癌患者进行术后辅助治疗是临床实践中的既定方法,与单纯手术相比,给予5-FU和左旋咪唑联合治疗一年将使五年总生存率提高约15%。尽管该方案仍然是当前的标准治疗方法,但辅助治疗的替代方案可能是术后仅给予半年的5-FU和亚叶酸,通过门静脉单独用5-FU进行为期7天的持续肝脏局部灌注,或在根治性切除后使用17-1A单克隆抗体免疫治疗。免疫治疗和化疗的联合目前正在临床研究中进行测试,可能会带来进一步的改善。未来结直肠癌辅助治疗的建议不仅将基于治疗效果,还必须考虑治疗成本。需要更好地界定辅助治疗的高危患者群体。