Chau I, Norman A R, Cunningham D, Tait D, Ross P J, Iveson T, Hill M, Hickish T, Lofts F, Jodrell D, Webb A, Oates J R
Royal Marsden Hospital, London and Surrey.
Ann Oncol. 2005 Apr;16(4):549-57. doi: 10.1093/annonc/mdi116. Epub 2005 Feb 2.
BACKGROUND: We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of protracted venous infusion (PVI) 5-fluorouracil (5-FU) against the standard bolus monthly regimen of 5-FU/leucovorin (LV) given for 6 months as adjuvant treatment in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with curatively resected stage II and III CRC were randomly assigned to 5-FU/LV [5-FU 425 mg/m(2) intravenously (i.v.) and LV 20 mg/m(2) i.v. bolus days 1-5 every 28 days for 6 months] or to PVI 5-FU (300 mg/m(2)/day for 12 weeks). RESULTS: Between 1993 and 2003, 801 eligible patients were randomised to 5-FU/LV (n=404) or PVI 5-FU (n=397). With a median follow-up of 5.3 years, 231 relapses and 220 deaths have been observed. Five-year relapse-free survival (RFS) was 66.7% [95% confidence interval (CI) 61.6% to 71.3%] and 73.3% (95% CI 68.4% to 77.6%) with bolus 5-FU/LV and PVI 5-FU, respectively [hazard ratio (HR) 0.8; 95% CI 0.62-1.04; P=0.10]. Five-year overall survival (OS) was 71.5% (95% CI 66.4% to 75.9%) and 75.7% (95% CI 70.8% to 79.9%) with bolus 5-FU/LV and PVI 5-FU, respectively (HR 0.79; 95% CI 0.61-1.03; P=0.083). There was a significant survival advantage for patients starting adjuvant chemotherapy within 8 weeks (P=0.044). Significantly less diarrhoea, stomatitis, nausea and vomiting, alopecia, lethargy, and neutropenia (all with P <0.0001) were seen with PVI 5-FU. CONCLUSIONS: There was no OS difference between the two arms, although PVI 5-FU was associated with a trend towards better RFS and OS compared with bolus 5-FU/LV, as well as significantly less toxicity. Based on our results, the probability of 12 weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low (P <0.005), and therefore shorter duration of adjuvant treatment should be explored further.
背景：我们进行了一项多中心随机试验，比较12周持续静脉输注（PVI）5-氟尿嘧啶（5-FU）与5-FU/亚叶酸钙（LV）标准大剂量每月方案（持续6个月）作为结直肠癌（CRC）辅助治疗的疗效和毒性。 患者与方法：接受根治性切除的II期和III期CRC患者被随机分配至5-FU/LV组[5-FU 425mg/m²静脉注射（i.v.），LV 20mg/m²静脉推注，第1 - 5天，每28天一次，共6个月]或PVI 5-FU组（300mg/m²/天，共12周）。 结果：1993年至2003年期间，801例符合条件的患者被随机分配至5-FU/LV组（n = 404）或PVI 5-FU组（n = 397）。中位随访5.3年，观察到231例复发和220例死亡。5年无复发生存率（RFS）在大剂量5-FU/LV组和PVI 5-FU组分别为66.7%[95%置信区间（CI）61.6%至71.3%]和73.3%（95%CI 68.4%至77.6%）[风险比（HR）0.8；95%CI 0.62 - 1.04；P = 0.10]。5年总生存率（OS）在大剂量5-FU/LV组和PVI 5-FU组分别为71.5%（95%CI 66.4%至75.9%）和75.7%（95%CI 70.8%至79.9%）（HR 0.79；95%CI 0.61 - 1.03；P = 0.083）。在8周内开始辅助化疗的患者有显著的生存优势（P = 0.044）。PVI 5-FU组出现的腹泻、口腔炎、恶心和呕吐、脱发、嗜睡及中性粒细胞减少显著更少（均P < 0.0001）。 结论：两组之间OS无差异，尽管与大剂量PVI 5-FU与大剂量5-FU/LV相比，有RFS和OS改善的趋势，且毒性显著更低。基于我们的结果，12周PVI 5-FU劣于6个月大剂量5-FU/LV的概率极低（P < 0.005），因此应进一步探索更短疗程的辅助治疗。
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