title: Weekly fluorouracil at 425 mg/m(2) plus low-dose folinic acid for 24 weeks as adjuvant treatment for colorectal cancer: assessment of toxicity and delivery.
abstract: OBJECTIVE
  To assess the toxicity and dose delivery of weekly bolus 5-fluorouracil (5-FU) at 425 mg/m(2) plus low-dose folinic acid (FA) for 24 weeks as adjuvant treatment for colorectal cancer.
  
  
  METHODS
  Data were collected on toxicity and dose reductions, stoppages, delays and intensity from 100 consecutive patients receiving this adjuvant regimen after curative surgery.
  
  
  RESULTS
  There were 53 men and 47 women (median age: 64 and 65 years, respectively); 77 patients with colon cancer and 23 with cancer of the rectum; 34 patients with Dukes' stage B and 66 with Dukes' stage C. Thirty-seven patients experienced at least one grade 3 or 4 toxicity, mainly diarrhoea (20 patients) or fatigue (14 patients). Only one grade 4 toxicity was noted (diarrhoea). In multivariate analysis, increased grade 3 and 4 toxicity was significantly associated with female gender (P = 0.001) and age >65 years (P = 0.046). Forty patients completed the 24 cycles without dose reduction or delay. Forty-one patients required at least one dose reduction. The median 'conventional' dose intensity (DI), calculated from the first cycle to the last, was 408 mg/m(2)/week (96%). The median DI over 24 weeks was 387 mg/m(2)/week (91%). A higher median 24-week DI was delivered to men (407 mg/m(2)/week, 96%) than women (361 mg/m(2)/ week, 85%; P = 0.009). Women older than 65 years showed a significantly reduced median DI over 24 weeks (347 mg/ m(2)/week, 82%) compared with men aged 65 years or younger (407 mg/m(2)/week, 96%; P = 0.049) and men older than 65 years (425 mg/m(2)/week, 100%; P = 0.001), although the difference against women aged 65 years or younger (377 mg/ m(2)/week, 89%) was not statistically significant (P = 0.09).
  
  
  CONCLUSIONS
  This regimen has shown what might be considered high rates of grade 3 and 4 toxicity for an adjuvant treatment, although the delivered DI was acceptable. Caution is urged in the treatment of elderly female patients who have statistically higher rates of grade 3 and 4 toxicity and lower DI.
authors.affiliation: Clatterbridge Centre for Oncology, Bebington, Wirral, UK.
authors.forename: V S
authors.initials: VS
authors.lastname: Ramani
authors.forename: S W
authors.initials: SW
authors.lastname: Gollins
authors.forename: H
authors.initials: H
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; 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; D010349:Patient Compliance; D028761:Withholding Treatment / Q000706:statistics & numerical data
chemical_list: D002955:Leucovorin; D005472:Fluorouracil