title: Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.
abstract: BACKGROUND
  Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken.
  
  
  METHODS
  Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines.
  
  
  RESULTS
  The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively.
  
  
  CONCLUSIONS
  L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Nobile
authors.forename: M C
authors.initials: MC
authors.lastname: Barzacch
authors.forename: O
authors.initials: O
authors.lastname: Sanguineti
authors.forename: S
authors.initials: S
authors.lastname: Chiara
authors.forename: A
authors.initials: A
authors.lastname: Gozza
authors.forename: M
authors.initials: M
authors.lastname: Vincenti
authors.forename: A
authors.initials: A
authors.lastname: Lavarello
authors.forename: P
authors.initials: P
authors.lastname: Cognein
authors.forename: R
authors.initials: R
authors.lastname: Lionetto
authors.forename: P L
authors.initials: PL
authors.lastname: Percivale
authors.forename: S
authors.initials: S
authors.lastname: Bertoglio
authors.forename: C
authors.initials: C
authors.lastname: Murolo
authors.forename: M
authors.initials: M
authors.lastname: Esposito
authors.forename: M O
authors.initials: MO
authors.lastname: Vannozzi
authors.forename: R
authors.initials: R
authors.lastname: Rosso
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil