title: Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.
abstract: The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.
authors.affiliation: Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Napoli, Italy. sdponco@unina.it
authors.forename: S
authors.initials: S
authors.lastname: De Placido
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: C
authors.initials: C
authors.lastname: Carlomagno
authors.forename: G
authors.initials: G
authors.lastname: Paoletti
authors.forename: S
authors.initials: S
authors.lastname: Palazzo
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: C
authors.initials: C
authors.lastname: Iannace
authors.forename: G P
authors.initials: GP
authors.lastname: Ianniello
authors.forename: F
authors.initials: F
authors.lastname: De Vita
authors.forename: C
authors.initials: C
authors.lastname: Ficorella
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: G
authors.initials: G
authors.lastname: Pistillucci
authors.forename: M
authors.initials: M
authors.lastname: Gemini
authors.forename: E
authors.initials: E
authors.lastname: Cortesi
authors.forename: V
authors.initials: V
authors.lastname: Adamo
authors.forename: N
authors.initials: N
authors.lastname: Gebbia
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: C
authors.initials: C
authors.lastname: Gallo
authors.forename: F
authors.initials: F
authors.lastname: Perrone
authors.forename: G
authors.initials: G
authors.lastname: Persico
authors.forename: A R
authors.initials: AR
authors.lastname: Bianco
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D007978:Levamisole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil