title: Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. Colorectal Cancer Working Party of the United Kingdom Medical Research Council.
abstract: OBJECTIVE
  To determine the effects of interferon alpha-2a (IFN alpha) on the efficacy and toxicity of fluorouracil (FUra) and leucovorin (LV) in patients with advanced colorectal cancer.
  
  
  METHODS
  Two hundred sixty chemotherapy-naive patients were randomized to FUra/LV alone or FUra/LV plus IFN alpha. All patients received: LV 200 mg/m2 intravenous (IV) infusion over 2 hours, then FUra 400 mg/m2 i.v. bolus plus 400 mg/m2 i.v. infusion over 22 hours, all repeated on day 2. Treatment was every 2 weeks for up to 12 cycles. Patients randomized to IFN alpha received 6 x 10(6) IU subcutaneously every 48 hours throughout. Objective response (OR) and toxicity were assessed conventionally; in addition, palliative benefit and adverse effects were assessed using quality-of-life (QoL) questionnaires.
  
  
  RESULTS
  There were no differences in OR rate, progression-free survival, or overall survival. OR rates in assessable patients were as follows: FUra/LV alone (n = 104), complete or partial response (OR) = 27%, no change (NC) = 34%; FUra/LV/IFN alpha (n = 101), OR = 28%, NC = 30%. Median survival was 10 months in both arms. Dose-limiting FUra toxicities were not significantly increased by co-administration of IFN alpha, and the delivered FUra dose-intensity was not significantly reduced. However, QoL was adversely affected: patients on IFN alpha were less likely to report improvement in pretreatment physical and psychologic symptoms, and more likely to report new or worsening symptoms.
  
  
  CONCLUSIONS
  IFN alpha, at a dose that impaired QoL, did not improve the efficacy of FUra/LV. The power of this trial is sufficient to exclude with 95% confidence a benefit of 15% in OR or 10 weeks in median survival. Accordingly, we cannot recommend the use of IFN alpha as a clinical modulator of FUra/LV in the treatment of advanced colorectal cancer.
authors.affiliation: Colorectal Cancer Working Party, United Kingdom Medical Research Council, London, United Kingdom. seymour@thecafe.co.uk
authors.forename: M T
authors.initials: MT
authors.lastname: Seymour
authors.forename: M L
authors.initials: ML
authors.lastname: Slevin
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: R D
authors.initials: RD
authors.lastname: James
authors.forename: J A
authors.initials: JA
authors.lastname: Ledermann
authors.forename: T J
authors.initials: TJ
authors.lastname: Perren
authors.forename: W A
authors.initials: WA
authors.lastname: McAdam
authors.forename: P G
authors.initials: PG
authors.lastname: Harper
authors.forename: J P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: M
authors.initials: M
authors.lastname: Nicholson
authors.forename: A M
authors.initials: AM
authors.lastname: Duffy
authors.forename: R J
authors.initials: RJ
authors.lastname: Stephens
authors.forename: S P
authors.initials: SP
authors.lastname: Stenning
authors.forename: I
authors.initials: I
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011788:Quality of Life; D011994:Recombinant Proteins; D012074:Remission Induction; D015996:Survival Rate; D006113:United Kingdom
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil