Final results of a phase III clinical trial on adjuvant intraportal infusion with heparin and 5-fluorouracil (5-FU) in resectable colon cancer (EORTC GITCCG 1983-1987). European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group

• Published in: European journal of cancer (1990) 1997-07, Vol.33 (8), p.1209
• Main Authors: Nitti, D, Wils, J, Sahmoud, T, Curran, D, Couvreur, M L, Lise, M, Rauschecker, H, dos Santos, J G, Stremmel, W, Roelofsen, F
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - therapeutic use; Chemotherapy, Adjuvant; Colonic Neoplasms - drug therapy; Colonic Neoplasms - surgery; Disease Progression; Disease-Free Survival; Drug Therapy, Combination; Female; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; Follow-Up Studies; Heparin - administration & dosage; Heparin - therapeutic use; Humans; Infusions, Intravenous; Male; Middle Aged; Portal Vein; Postoperative Complications; Survival Rate
• ISSN: 0959-8049

In this phase III clinical trial conducted by the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer (GITCCG-EORTC), we evaluated the effect of adjuvant intraportal infusion of heparin (HEP) and 5-fluorouracil (5-FU) on overall survival, disease-free survival and time to progression in patients with resectable colon cancer. From January 1983 to June 1987, 235 patients were randomised from 14 institutions in seven European countries: 79 patients made up the control group (control): 72 the portal vein infusion group given heparin alone (5000 IU daily x 7 consecutive days) (HEP); 84 the portal vein infusion group given heparin (5000 IU daily x 7 consecutive days) and 5-FU (500 mg/m2 daily x 7 consecutive days) (HEP/5-FU); 34 patients were considered ineligible. The 199 patients considered eligible were well balanced for age, sex, Karnofsky index, tumour location, surgery, surgical procedure and Dukes' stage. Four patients (2 control, 1 HEP, 1 HEP/5-FU) died of surgical complications. No differences were observed between control group and treatment groups (HEP, HEP/5-FU) for postoperative complications and number of hospitalisation days. Severe toxicity (grade 3-4, WHO) was found in 12% of patients in the HEP group and 8% in the HEP/5-FU group. After a median follow-up of 9 years, disease progression was reported in 40% of patients in the control group, 40% in the HEP group and 29% in the HEP/5-FU group. Five-year survival, time to progression and disease-free survival were 69%, 58% and 56%, respectively, in the control arm, 61%, 58% and 56% in the HEP arm, and 71%, 69% and 65% in the HEP/5-FU arm. Based on all randomised patients, the effect of treatment was not statistically significant with respect to any of the endpoints. It is confirmed that intraportal 5-FU infusion is safe and has a tolerable toxicity, but cannot be considered standard treatment for patients with resectable colon cancer.