Borner M M, Castiglione M, Bacchi M, Weber W, Herrmann R, Fey M F, Pagani O, Leyvraz S, Morant R, Pestalozzi B, Hanselmann S, Goldhirsch A
Institute of Medical Oncology, Bern, Switzerland.
Ann Oncol. 1998 May;9(5):535-41. doi: 10.1023/a:1008270916325.
A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fluorouracil in both treatment arms.
Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU alone.
Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events.
This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with low-dose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
多种氟尿嘧啶（FU）联合亚叶酸钙（LV）的给药方案在晚期结直肠癌治疗中广泛应用于临床。仅北中部癌症治疗组采用的每月低剂量LV联合FU方案显示出相对于单纯使用FU有持久的生存获益（《临床肿瘤学杂志》1989年；7：1407 - 1417）。瑞士癌症组采用该方案进行一项验证性III期试验，但在两个治疗组中使用相同剂量强度的氟尿嘧啶。
不可切除或转移性结直肠癌患者被随机分为两组，一组接受每月FU 400 mg/m²/天联合LV 20 mg/m²/天，静脉推注，每日一次，共五天；另一组仅接受FU。
随机分组的310例患者中有309例符合条件并纳入分析。可测量疾病患者的客观缓解率在单纯FU组为9%，在FU联合LV组为22%（P = 0.0001）。无进展生存期的中位数分别为3.9个月和6.2个月（P = 0.003），总生存期分别为10个月和12.4个月（P = 0.02）。生存的主要预后因素为体能状态、体重减轻和疾病症状。WHO > 2级毒性反应，包括口腔炎（P = 0.001）、腹泻（P = 0.001）和恶心（P = 0.001），在FU联合LV组更为明显，但无致命事件。
这是已发表的在晚期结直肠癌中比较FU联合LV与单纯FU的最大规模随机试验。它证实了每月使用低剂量LV对FU进行生物调节可带来生存获益。FU联合LV的毒性作用对大多数患者来说是可接受的，并且患者对FU剂量减少反应良好。在缺乏理想的高剂量强度FU单药治疗方案的情况下，每月使用低剂量LV的FU方案为在晚期结直肠癌治疗中实现足够的FU疗效提供了一种简单且经济的方法。
