title: Phase III randomized study to compare interferon alfa-2a in combination with fluorouracil versus fluorouracil alone in patients with advanced colorectal cancer.
abstract: OBJECTIVE
  To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a ([IFN alpha 2a] Roferon-A; Hoffmann-LaRoche, Basel, Switzerland) versus 5-FU alone in the treatment of advanced colorectal cancer (ACC).
  
  
  METHODS
  A total of 245 previously untreated ACC patients were randomized to receive either IFN alpha 2a (9 million IU) subcutaneously (SC) three times weekly with 5-FU (750 mg/m2/d) by continuous intravenous (CIV) infusion on days 1 to 5 and then, after a 1-week hiatus, as a weekly IV bolus at the same dose (IFN/ 5-FU), or 5-FU alone at the same dose schedule (5-FU).
  
  
  RESULTS
  There were no significant differences between IFN/5-FU and 5-FU alone in the overall response rate (24% v 17%, P = .2), duration of response (median, 6.4 v 8.1 months), time to response (plateau at 3 months), time to progressive disease ([PD] median, 4.8 v 4.9 months), or survival duration (median, 13.9 v 13.2 months). Toxicity profiles were not statistically different except for constitutional symptoms, which were more frequent and more severe with IFN/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/ 5-FU (34%) than with 5-FU alone (21%) (P = .03). The number of deaths (mostly unrelated to drug treatment) during the study (8%) was similar with both regimens.
  
  
  CONCLUSIONS
  The combination IFN/5-FU produced a response rate, response duration, and survival duration similar to that of 5-FU alone. The addition of IFN to 5-FU in the doses and schedules used in this study did not provide any further benefit over 5-FU alone and cannot be recommended for patients with metastatic ACC. This study confirms the value of large prospective randomized clinical trials to determine the clinical value of regimens that emerge from smaller single-center phase II studies.
authors.affiliation: Roche International Clinical Research Center, Lingolsheim, France.
authors.forename: F A
authors.initials: FA
authors.lastname: Greco
authors.forename: R
authors.initials: R
authors.lastname: Figlin
authors.forename: M
authors.initials: M
authors.lastname: York
authors.forename: L
authors.initials: L
authors.lastname: Einhorn
authors.forename: R
authors.initials: R
authors.lastname: Schilsky
authors.forename: E M
authors.initials: EM
authors.lastname: Marshall
authors.forename: S S
authors.initials: SS
authors.lastname: Buys
authors.forename: M J
authors.initials: MJ
authors.lastname: Froimtchuk
authors.forename: J
authors.initials: J
authors.lastname: Schuller
authors.forename: L
authors.initials: L
authors.lastname: Schuchter
authors.forename: M
authors.initials: M
authors.lastname: Buyse
authors.forename: L
authors.initials: L
authors.lastname: Ritter
authors.forename: A
authors.initials: A
authors.lastname: Man
authors.forename: A K
authors.initials: AK
authors.lastname: Yap
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012074:Remission Induction
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil