title: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer.
abstract: BACKGROUND
  In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial.
  
  
  METHODS
  Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio.
  
  
  RESULTS
  189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group.
  
  
  CONCLUSIONS
  Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.
authors.affiliation: Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: S
authors.initials: S
authors.lastname: Pyrhönen
authors.forename: R D
authors.initials: RD
authors.lastname: James
authors.forename: C J
authors.initials: CJ
authors.lastname: Punt
authors.forename: T F
authors.initials: TF
authors.lastname: Hickish
authors.forename: R
authors.initials: R
authors.lastname: Heikkila
authors.forename: T B
authors.initials: TB
authors.lastname: Johannesen
authors.forename: H
authors.initials: H
authors.lastname: Starkhammar
authors.forename: C A
authors.initials: CA
authors.lastname: Topham
authors.forename: L
authors.initials: L
authors.lastname: Awad
authors.forename: C
authors.initials: C
authors.lastname: Jacques
authors.forename: P
authors.initials: P
authors.lastname: Herait
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care; D011336:Probability; D011788:Quality of Life; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin