Randomised Trial of Irinotecan Plus Supportive Care Versus Supportive Care Alone After Fluorouracil Failure for Patients With Metastatic Colorectal Cancer

Lancet. 1998 Oct 31;352(9138):1413-8. doi: 10.1016/S0140-6736(98)02309-5.

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / therapeutic use*
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Palliative Care
  • Probability
  • Quality of Life
  • Survival Analysis
  • Treatment Failure

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Fluorouracil
  • Camptothecin