Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: Combined analysis of 2,691 patients in randomized controlled trials

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Gunnar Folprecht - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Matthew T Seymour - (Author)
  • Leonard Saltz - (Author)
  • Jean-Yves Douillard - (Author)
  • Hartmut Hecker - (Author)
  • Richard J Stephens - (Author)
  • Timothy S Maughan - (Author)
  • Eric Van Cutsem - (Author)
  • Philippe Rougier - (Author)
  • Emmanuel Mitry - (Author)
  • Ute Schubert - (Author)
  • Claus-Henning Köhne - (Author)

Abstract

PURPOSE: Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC).

PATIENTS AND METHODS: Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age > or = 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients.

RESULTS: Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and > or = 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable.

CONCLUSION: Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.

Details

Original languageEnglish
Pages (from-to)1443-1451
Number of pages9
JournalJournal of Clinical Oncology
Volume26
Issue number9
Publication statusPublished - 20 Mar 2008
Peer-reviewedYes

Conference

Title43rd Annual Meeting of the American-Society-of-Clinical-Oncology
Duration1 - 5 June 2007
CityChicago
CountryIsrael

External IDs

Scopus 41149180580
PubMed 18349394
WOS 000254178600010
ORCID /0000-0002-9321-9911/work/142251933

Keywords

Sustainable Development Goals

Keywords

  • Elderly-patients, Adjuvant chemotherapy, Clinical-trials, Pooled analysis, Colon-cancer, Fluorouracil failure, Continuous-infusion, Irinotecan, Leucovorin, Oxaliplatin