title: 5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of metastatic colorectal carcinoma. A randomized study.
abstract: BACKGROUND
  In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN.
  
  
  METHODS
  105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week.
  
  
  RESULTS
  After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05).
  
  
  CONCLUSIONS
  5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.
authors.affiliation: Département d'Oncologie, Hôpitaux Universitaires de Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Dufour
authors.forename: F
authors.initials: F
authors.lastname: Husseini
authors.forename: B
authors.initials: B
authors.lastname: Dreyfus
authors.forename: H
authors.initials: H
authors.lastname: Cure
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Prevost
authors.forename: J P
authors.initials: JP
authors.lastname: Olivier
authors.forename: F
authors.initials: F
authors.lastname: Dumas
authors.forename: B
authors.initials: B
authors.lastname: Duclos
authors.forename: R
authors.initials: R
authors.lastname: Olivares
authors.forename: A
authors.initials: A
authors.lastname: Leszler
authors.forename: J P
authors.initials: JP
authors.lastname: Bergerat
authors.forename: B
authors.initials: B
authors.lastname: Audhuy
authors.forename: L
authors.initials: L
authors.lastname: Thill
authors.forename: F
authors.initials: F
authors.lastname: Oberling
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010349:Patient Compliance; D011994:Recombinant Proteins
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil