title: A phase III study of 5-fluorouracil versus 5-fluorouracil plus interferon alpha 2b versus 5-fluorouracil plus leucovorin in patients with advanced colorectal cancer: a Hellenic Cooperative Oncology Group (HeCOG) study.
abstract: We conducted a phase III study in patients with advanced colorectal carcinoma (ACC). The total number of patients randomized from October 1993 until July 1998 was 192, whereas therapy was started on 179 and 158 (82.3%) have been evaluable. The treatment schedules consisted of weekly bolus administration for 6 weeks of 5-fluorouracil (5-FU), 600 mg/m2 (arm I) versus 5-FU (500 mg/m2) intravenous bolus and interferon-alpha, 5 MU subcutaneously, three times a week (arm II) versus leucovorin 200 mg/m2 in 2-hour infusion and 5-FU 500 mg/m2 intravenous bolus at the midtime of leucovorin infusion (arm III) followed by a 2-week rest period. Treatment was continued for six cycles or until progression. This study failed to show any superiority of the modulated 5-FU versus single administration of 5-FU. There were no significant differences between the three arms in the overall response rate (10.3% versus 11.3% versus 12.9%, p = 0.95), the time to tumor progression (median, 3.9 versus 3.8 versus 6.0 months, p = 0.59), or survival duration (median, 14.7 versus 12.4 versus 16.3 months, p = 0.71). The incidence of severe (grades III and IV) toxicity was significantly higher in patients in arm II and III (24.5% and 18.6%) versus arm I (6.0%) (p = 0.01). Because modulated 5-FU failed to show superiority versus 5-FU, new agents and new strategies are needed for the treatment of advanced colorectal carcinoma.
authors.affiliation: Department of Medicine/Oncology, University Hospital of Patras, Rion 26500, Greece.
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
authors.forename: Costas
authors.initials: C
authors.lastname: Nicolaides
authors.forename: Epaminondas
authors.initials: E
authors.lastname: Samantas
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Mylonakis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Gennatas
authors.forename: Georgios
authors.initials: G
authors.lastname: Kouvatseas
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Giannoulis
authors.forename: Christos
authors.initials: C
authors.lastname: Dervenis
authors.forename: Georgios
authors.initials: G
authors.lastname: Basdanis
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Pavlidis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Androulakis
authors.forename: Georgios
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil