title: Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection.
abstract: BACKGROUND
  Current standard therapy following resection of high-risk colon cancer is intravenous bolus 5-fluorouracil (5-FU) with leucovorin (LV), but there is no consensus on the optimum regimen of these drugs: practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule. We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity.
  
  
  METHODS
  One hundred and sixty-two patients were studied: 60% male; median age 65 years (36% over 70 years); 94% colorectal primary. Treatment was intravenous bolus (5 min) 5-FU 425 mg/m(2) plus D,L-LV 45 mg flat rate once weekly, for a planned 24 weeks. Data for toxicity, dose-reductions, delays and stoppages were collected.
  
  
  RESULTS
  Overall, 20% of patients experienced any grade > or = 3 toxicity, most commonly diarrhoea (14% patients). Dose reductions were made in 35% of patients (although only 21% required 20% or more reduction); toxicity contributed to a decision to stop treatment before 24 weeks in 16% of patients. Median delivered dose intensity (DI) was 96% of planned (407 mg/m(2)/week) during treatment, and 91% of planned (385 mg/m(2)/week) over the full 24 week treatment plan. Female sex and age >70 years were significantly associated with higher rates of toxicity and dose adjustment, and lower delivered DI.
  
  
  CONCLUSIONS
  Weekly treatment at these doses is convenient and well-tolerated for the large majority of patients, and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic standard regimens.
authors.affiliation: Cancer Research UK Clinical Centre, Cookridge Hospital Leeds, Leeds LS16 6QB, UK.
authors.forename: K
authors.initials: K
authors.lastname: Patel
authors.forename: D A
authors.initials: DA
authors.lastname: Anthoney
authors.forename: A M
authors.initials: AM
authors.lastname: Crellin
authors.forename: D
authors.initials: D
authors.lastname: Sebag-Montefiore
authors.forename: J
authors.initials: J
authors.lastname: Messruther
authors.forename: M T
authors.initials: MT
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil