TY - JOUR
T1 - Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer
T2 - Evidence in terms of response rate by the advanced colorectal cancer meta-analysis project
AU - Piedbois, P.
AU - Buyse, M.
AU - Rustum, Y.
AU - Machover, D.
AU - Erlichman, C.
AU - Carlson, R. W.
AU - Valone, F.
AU - Labianca, R.
AU - Doroshow, J. H.
AU - Petrelli, N.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.1992.10.6.896
DO - 10.1200/JCO.1992.10.6.896
M3 - Article
C2 - 1534121
AN - SCOPUS:0026721532
SN - 0732-183X
VL - 10
SP - 896
EP - 903
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -