Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate by the advanced colorectal cancer meta-analysis project

P. Piedbois, M. Buyse, Y. Rustum, D. Machover, C. Erlichman, R. W. Carlson, F. Valone, R. Labianca, J. H. Doroshow, N. Petrelli

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Abstract

Purpose: A meta-analysis was performed on nine randomized clinical trials that compared fluorouracil (5-FU) with 5-FU plus intravenous (IV) leucovorin (LV) for the treatment of advanced colorectal cancer. Design: The analysis was based on the most recently updated individual patient data from all trials. The end points of interest were tumor response and overall survival. Results: Therapy with 5-FU plus LV administered either as weekly or monthly regimens showed a highly significant benefit over single-agent 5-FU in terms of tumor response rate (23% v 11%; response odds ratio (OR), 0.45; P < 10-7). This increase in response did not result in a discernable improvement of overall survival (survival OR, 0.97; P = .57). The large number of patients who did not respond to treatment in both groups, and cross-overs from 5-FU alone to 5-FU plus LV are discussed as plausible explanations for the lack of a survival difference. Conclusion: These results confirm the advantage of 5-FU plus leucovorin over 5-FU alone in terms of objective tumor response. They also suggest that in planning future trials, tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer.

Original languageEnglish (US)
Pages (from-to)896-903
Number of pages8
JournalJournal of Clinical Oncology
Volume10
Issue number6
DOIs
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Piedbois, P., Buyse, M., Rustum, Y., Machover, D., Erlichman, C., Carlson, R. W., Valone, F., Labianca, R., Doroshow, J. H., & Petrelli, N. (1992). Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate by the advanced colorectal cancer meta-analysis project. Journal of Clinical Oncology, 10(6), 896-903. https://doi.org/10.1200/JCO.1992.10.6.896