A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer: evolution of a Regimen

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• 作者：de Gramont ; A. ; Louvet ; C. ; André ; T. ; Tournigand ; C. ; Krulik ; M.
• 关键词：leucovorin ; 5-fluorouracil ; colorectal cancer ; continuous infusion ; GERCOD
• 刊名：European Journal of Cancer
• 出版年：1998
• 期刊代码：88_09598049
• 类别：med
• 出版时间：April, 1998
• 卷：34
• 期：5
• 页码：619-626
• 文件大小：200 K

摘要

The addition of leucovorin (LV) to 5-fluorouracil (5-FU) in advanced colorectal cancer has shown improved tumour response rates in many trials, but the optimal LV/5-FU regimen has yet to be determined. Seven studies carried out over the last 12 years to evaluate the safety and efficacy of various LV/5-FU regimens are reviewed. The initial bimonthly high-dose LV/5-FU regimen consisted of high-dose LV as a 2-h infusion followed by 5-FU as an intravenous (i.v.) bolus plus a 22-h continuous infusion (CI), repeated for two consecutive days every 2 weeks. A randomised comparison of this bimonthly high-dose LV/5-FU regimen and the NCCTG–Mayo Clinic regimen (LV [20mg/m²/day] followed by 5-FU bolus [425mg/m²/day] daily ×5, every 4 weeks) showed that the bimonthly high-dose LV/5-FU regimen was superior to the NCCTG–Mayo Clinic regimen in response rate and progression-free survival, but showed no difference in overall survival. In addition, toxicity was less with the bimonthly high-dose LV/5-FU regimen. These promising results led to a phase II trial of a simplified bimonthly high-dose LV/5-FU regimen consisting of LV (500mg/m²/day) and a 48-h CI of 5-FU (1.5–2g/m²/day) which has been administered alone or in combination. In summary, GERCOD-sponsored studies have further demonstrated that higher doses of both LV and 5-FU given as a CI can improve response rates still more with acceptable toxicity. Further studies are focused on the effectiveness of combination with oxaliplatin or CPT-11 in metastatic disease and the use of high-dose LV/5-FU regimens for colorectal cancer in the adjuvant setting.