title: A prospective randomised trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer.
abstract: BACKGROUND
  To compare protracted venous infusion (PVI) 5-fluorouracil (5-FU) with and without mitomycin C (MMC) in a prospectively randomised study and analyse for tumour response, survival, toxicity and quality of life (QL).
  
  
  METHODS
  Two hundred patients with advanced colorectal cancer received PVI 5-FU 300 mg/m2/day for a maximum of 24 weeks and were randomised to PVI 5-FU alone or PVI 5-FU + MMC 10 mg/m2 (7 mg/m2 from June 1995) 6 weekly for 4 courses.
  
  
  RESULTS
  Overall response was 54% (95% confidence interval [CI] 44.1%-63.9%) with PVI 5-FU + MMC compared to 38% (95% CI: 28.3%-47.7%) for PVI 5-FU alone (P = 0.024). The median failure free survival was 7.9 months in PVI 5-FU plus MMC and 5.4 months with PVI 5-FU alone (P = 0.033) and at one year 31.9% for the combination compared to 17.7% for PVI 5-FU alone. Median survival was 14 months with MMC and 15 months in 5-FU alone; one-year survival 51.7% vs. 57.2%. PVI 5-FU + MMC caused more overall haematological toxicity but CTC grades 3/4 was increased only for thrombocytopaenia. Two patients treated with a cumulative dose of MMC of 40 mg/m2 developed haemolytic uraemic syndrome warranting the reduction in cumulative MMC dose to 28 mg/m2. The global QL scores were better for PVI 5-FU + MMC arm at 24 weeks, but the remaining QL data showed no differences.
  
  
  CONCLUSIONS
  PVI 5-FU + MMC results in failure-free survival and response advantage, tolerable toxicity and better QL when compared to PVI 5-FU alone but no overall survival advantage. There is no irreversible toxicity with MMC at a cumulative dose of 28 mg/m2.
authors.affiliation: Department of Medicine, The Royal Marsden Hospital, London and Sutton, Surrey, UK.
authors.forename: P
authors.initials: P
authors.lastname: Ross
authors.forename: A
authors.initials: A
authors.lastname: Norman
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: A
authors.initials: A
authors.lastname: Webb
authors.forename: T
authors.initials: T
authors.lastname: Iveson
authors.forename: A
authors.initials: A
authors.lastname: Padhani
authors.forename: J
authors.initials: J
authors.lastname: Prendiville
authors.forename: M
authors.initials: M
authors.lastname: Watson
authors.forename: A
authors.initials: A
authors.lastname: Massey
authors.forename: R
authors.initials: R
authors.lastname: Popescu
authors.forename: J
authors.initials: J
authors.lastname: Oates
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002405:Catheterization, Central Venous; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage; D011446:Prospective Studies; D011788:Quality of Life; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D008937:Mitomycins; D005472:Fluorouracil