title: Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.
abstract: BACKGROUND
  It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-alpha and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer.
  
  
  OBJECTIVE
  To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer.
  
  
  METHODS
  From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m(2)/week x 6, followed by a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients).
  
  
  RESULTS
  A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received > or =80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer.
authors.affiliation: 1st Department of Internal Medicine, Oncology Section, AHEPA Hospital, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece. fountzil@med.auth.gr
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: A
authors.initials: A
authors.lastname: Zisiadis
authors.forename: U
authors.initials: U
authors.lastname: Dafni
authors.forename: C
authors.initials: C
authors.lastname: Konstantaras
authors.forename: G
authors.initials: G
authors.lastname: Hatzitheoharis
authors.forename: S
authors.initials: S
authors.lastname: Papavramidis
authors.forename: A
authors.initials: A
authors.lastname: Bousoulegas
authors.forename: G
authors.initials: G
authors.lastname: Basdanis
authors.forename: E
authors.initials: E
authors.lastname: Giannoulis
authors.forename: J
authors.initials: J
authors.lastname: Dokmetzioglou
authors.forename: C
authors.initials: C
authors.lastname: Katsohis
authors.forename: E
authors.initials: E
authors.lastname: Nenopoulou
authors.forename: N
authors.initials: N
authors.lastname: Karvounis
authors.forename: E
authors.initials: E
authors.lastname: Briassoulis
authors.forename: G
authors.initials: G
authors.lastname: Aravantinos
authors.forename: P
authors.initials: P
authors.lastname: Kosmidis
authors.forename: D
authors.initials: D
authors.lastname: Skarlos
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil