Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research

Lancet. 1998 Jun 6;351(9117):1677-81. doi: 10.1016/s0140-6736(97)08169-5.

Abstract

Background: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days).

Methods: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat.

Findings: 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% Cl for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%).

Interpretation: PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / surgery*
  • Disease Progression
  • Drug Combinations
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / therapeutic use
  • Heparin / administration & dosage*
  • Heparin / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / mortality
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary*
  • Male
  • Portal Vein
  • Proportional Hazards Models
  • Prospective Studies
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / surgery*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Anticoagulants
  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Heparin
  • Fluorouracil