Köhne C-H, Wils J, Lorenz M, Schöffski P, Voigtmann R, Bokemeyer C, Lutz M, Kleeberg C, Ridwelski K, Souchon R, El-Serafi M, Weiss U, Burkhard O, Rückle H, Lichnitser M, Langenbuch T, Scheithauer W, Baron B, Couvreur M L, Schmoll H J
Department og Internal Medicine I, University of Dresden, Dresden, Germany.
J Clin Oncol. 2003 Oct 15;21(20):3721-8. doi: 10.1200/JCO.2003.11.122. Epub 2003 Sep 8.
PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.
目的：本试验旨在确定每周24小时输注的高剂量氟尿嘧啶（FU）是否比推注FU+亚叶酸钙（LV）更具活性，以及高剂量输注FU是否可被LV调节。 患者与方法：共497例既往未接受治疗的转移性结直肠癌患者被随机分配接受以下治疗：在第1至5天静脉推注FU 425mg/m²+LV 20mg/m²，并在第28天重复（FU+LV）；或单独24小时输注FU 2600mg/m²（FU24h），或与500mg/m² LV联合使用（FU24h+LV），均每周给药x6，随后休息2周。生存是主要研究终点。 结果：中位随访超过3年，各治疗组的生存率无差异（中位FU+LV，11.1个月[95%CI，10.2至15.0个月]；FU24h，13.0个月[95%CI，10.4至15.4个月]；FU24h+LV，13.7个月[95%CI，12.0至16.4个月]；P=0.724）。FU24h+LV的无进展生存期（PFS）显著更长（中位FU+LV，4.0个月[95%CI，3.4至4.9]；FU24h，4.1个月[95%CI，3.4至5.0]；FU24h+LV 5.6个月[95%CI，4.4至6.7]；P=0.029）。可测量疾病患者亚组的缓解率分别为：FU+LV组12%、FU24h组10%、FU24h+LV组17%（无显著性差异）。与FU24h组（6%）或FU+LV组（9%）相比，FU24h+LV组3/4级腹泻的发生率更高（22%）；然而，推注FU+LV组的口腔炎（FU+LV组11%，FU24h组3%，FU24h+LV组5%）和血液学毒性更高。三组的总体生活质量无差异。 结论：相对于推注FU+LV，FU24h+LV和FU24h均未延长生存期。亚叶酸钙添加到FU24h中可增加PFS，但会增加毒性。
Biology (Basel). 2021-10-29
Int J Colorectal Dis. 2018-9
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