Wils J
The Laurentius Hospital, Roermond, The Netherlands.
Br J Cancer. 1998;77 Suppl 2(Suppl 2):23-8. doi: 10.1038/bjc.1998.422.
After many years, during which the assumption prevailed that adjuvant chemotherapy was of no benefit in patients with resectable adenocarcinoma of the colon, findings of several large USA studies published from the late 1980s have caused a marked shift in surgical and medical opinion. Although results in patients with Dukes' B disease have not shown any clear benefit, the efficacy of adjuvant chemotherapy has nevertheless been shown in those with Dukes' C colon cancer. As a result, the Mayo regimen of 5-fluorouracil (5-FU) with low-dose leucovorin (LV) has become accepted as standard adjuvant therapy in these patients. However, the disadvantages associated with standard 5-FU-based treatment, particularly those relating to its toxicity and inconvenience of administration, have generated interest in other regimens and agents. The novel direct and specific thymidylate synthase inhibitor raltitrexed ('Tomudex') has been associated with similar objective response rates to standard therapy with 5-FU plus LV in patients with advanced colorectal cancer. In addition, raltitrexed has an attractive tolerability profile compared with that of 5-FU plus LV (specifically with respect to lower incidences of mucositis and leucopenia), and the simple 3-weekly administration schedule may be considered more convenient by many patients and may reduce healthcare resource consumption. To investigate alternatives to the Mayo regimen in the adjuvant treatment of Dukes' C adenocarcinoma of the colon, two large European trials have been set up: (1) PETACC-1 (first Pan-European Trial for Adjuvant Treatment of Colon Cancer), to compare raltitrexed with the Mayo regimen of 5-FU and low-dose LV; (2) PETACC-2 (second Pan-European Trial), to compare the Mayo regimen with three regimens in which 5-FU is given by prolonged infusion. These trials will provide valuable international data to add to those from the USA and will assess the place of raltitrexed in the adjuvant treatment of Dukes' C colon cancer. They will also compare directly for the first time infusional and bolus 5-FU regimens in the adjuvant setting.
多年来，人们普遍认为辅助化疗对可切除的结肠癌患者没有益处，但自20世纪80年代末以来美国发表的几项大型研究结果使外科和医学观点发生了显著转变。虽然在Dukes' B期疾病患者中未显示出明显益处，但辅助化疗在Dukes' C期结肠癌患者中已显示出疗效。因此，5-氟尿嘧啶（5-FU）联合低剂量亚叶酸（LV）的梅奥方案已成为这些患者公认的标准辅助治疗方法。然而，基于标准5-FU治疗的缺点，特别是其毒性和给药不便，引发了对其他方案和药物的兴趣。新型直接特异性胸苷酸合成酶抑制剂雷替曲塞（“拓优得”）在晚期结直肠癌患者中的客观缓解率与5-FU加LV的标准治疗相似。此外，与5-FU加LV相比，雷替曲塞具有更具吸引力的耐受性（特别是粘膜炎和白细胞减少发生率较低），许多患者可能认为简单的每3周给药方案更方便，并且可能减少医疗资源消耗。为了研究在Dukes' C期结肠癌辅助治疗中替代梅奥方案的方法，已经开展了两项大型欧洲试验：（1）PETACC-1（第一项结肠癌辅助治疗泛欧试验），比较雷替曲塞与5-FU和低剂量LV的梅奥方案；（2）PETACC-2（第二项泛欧试验），比较梅奥方案与三种5-FU持续输注方案。这些试验将提供有价值的国际数据，补充美国的相关数据，并评估雷替曲塞在Dukes' C期结肠癌辅助治疗中的地位。它们还将首次在辅助治疗环境中直接比较5-FU持续输注和推注方案。
