title: 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.
abstract: 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.
authors.affiliation: Istituto di Clinica Chirurgica II, Università di Padova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Nitti
authors.forename: J
authors.initials: J
authors.lastname: Wils
authors.forename: T
authors.initials: T
authors.lastname: Sahmoud
authors.forename: D
authors.initials: D
authors.lastname: Curran
authors.forename: M L
authors.initials: ML
authors.lastname: Couvreur
authors.forename: M
authors.initials: M
authors.lastname: Lise
authors.forename: H
authors.initials: H
authors.lastname: Rauschecker
authors.forename: J G
authors.initials: JG
authors.lastname: dos Santos
authors.forename: W
authors.initials: W
authors.lastname: Stremmel
authors.forename: F
authors.initials: F
authors.lastname: Roelofsen
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D011183:Postoperative Complications; D015996:Survival Rate
chemical_list: D000925:Anticoagulants; D000964:Antimetabolites, Antineoplastic; D006493:Heparin; D005472:Fluorouracil