TY - JOUR
T1 - Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin
T2 - Interim results of a phase III trial
AU - Rothenberg, Mace L.
AU - Oza, Amit M.
AU - Bigelow, Robert H.
AU - Berlin, Jordan D.
AU - Marshall, John L.
AU - Ramanathan, Ramesh K.
AU - Hart, Lowell L.
AU - Gupta, Sunil
AU - Garay, Carlos A.
AU - Burger, Brent G.
AU - Le Bail, Nathalie
AU - Haller, Daniel G.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Purpose: In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL). Patients and Methods: Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients. Results: Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher's exact test, P < .0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P < .0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (χ2 test, P < .001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate. Conclusion: For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.
AB - Purpose: In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL). Patients and Methods: Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients. Results: Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher's exact test, P < .0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P < .0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (χ2 test, P < .001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate. Conclusion: For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.
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U2 - 10.1200/JCO.2003.11.126
DO - 10.1200/JCO.2003.11.126
M3 - Article
C2 - 12775730
AN - SCOPUS:0037531121
SN - 0732-183X
VL - 21
SP - 2059
EP - 2069
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -