5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer

Eur J Cancer. 1997 Oct;33(11):1789-93. doi: 10.1016/s0959-8049(97)00175-5.

Abstract

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary*
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / adverse effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Survival Analysis
  • Survival Rate

Substances

  • Antimetabolites, Antineoplastic
  • Fluorouracil