TY - JOUR
T1 - A four-arm, randomized, multicenter phase II trial of oxaliplatin combined with varying schedules of 5-fluorouracil as first-line therapy in previously untreated advanced colorectal cancer
AU - Ramanathan, Ramesh K.
AU - Bjarnason, Georg A.
AU - Bernard, Stephen Alan
AU - Desimone, Philip
AU - Braich, Theodore
AU - Evers, Joseph P.
AU - Hrushesky, William J.
AU - Jolivet, Jacques
PY - 2008/3
Y1 - 2008/3
N2 - Background: Oxaliplatin combined with 5-fluorouracil (5-FU), with or without leucovorin (LV), is effective and well tolerated for first-line therapy of advanced colorectal cancer (CRC). However, there is no consensus as to which oxaliplatin/5-FU-containing regimen is superior in the first-line setting.This randomized, multicenter phase II trial was designed to evaluate and compare the efficacy of 4 different oxaliplatin/5-FU regimens. Patients and Methods: Patients with previously untreated metastatic CRC (mCRC; n = 129) were randomized to 1 of 4 treatment regimens: (1) continuous 5-FU infusion plus oxaliplatin (n = 23); (2) weekly 5-FU bolus with LV plus oxaliplatin (n = 40); (3) oxaliplatin with 2-day infusion 5-FU/LV (FOLFOX4, n = 41); and (4) chronomodulated 5-FU plus oxaliplatin (n = 25). Results: Overall response rates, after expert assessment, ranged from 24% to 34%, and median progression-free survival (PFS) ranged from 6 months to 8 months. Although no significant differences in efficacy were detected in pair-wise comparisons of the 4 different regimens, patients randomized to FOLFOX4 had the highest response rate and longest PFS. The FOLFOX4 regimen was also associated with the lowest incidence of severe (grade 3/4) toxicity, with the exception of cumulative peripheral neurotoxicity. Conclusion: This randomized phase II trial provides evidence that oxaliplatin/5-FU regimens are effective and well tolerated for first-line therapy of previously untreated mCRC. The FOLFOX regimens are now an established standard for CRC.
AB - Background: Oxaliplatin combined with 5-fluorouracil (5-FU), with or without leucovorin (LV), is effective and well tolerated for first-line therapy of advanced colorectal cancer (CRC). However, there is no consensus as to which oxaliplatin/5-FU-containing regimen is superior in the first-line setting.This randomized, multicenter phase II trial was designed to evaluate and compare the efficacy of 4 different oxaliplatin/5-FU regimens. Patients and Methods: Patients with previously untreated metastatic CRC (mCRC; n = 129) were randomized to 1 of 4 treatment regimens: (1) continuous 5-FU infusion plus oxaliplatin (n = 23); (2) weekly 5-FU bolus with LV plus oxaliplatin (n = 40); (3) oxaliplatin with 2-day infusion 5-FU/LV (FOLFOX4, n = 41); and (4) chronomodulated 5-FU plus oxaliplatin (n = 25). Results: Overall response rates, after expert assessment, ranged from 24% to 34%, and median progression-free survival (PFS) ranged from 6 months to 8 months. Although no significant differences in efficacy were detected in pair-wise comparisons of the 4 different regimens, patients randomized to FOLFOX4 had the highest response rate and longest PFS. The FOLFOX4 regimen was also associated with the lowest incidence of severe (grade 3/4) toxicity, with the exception of cumulative peripheral neurotoxicity. Conclusion: This randomized phase II trial provides evidence that oxaliplatin/5-FU regimens are effective and well tolerated for first-line therapy of previously untreated mCRC. The FOLFOX regimens are now an established standard for CRC.
KW - Chronomodulated regimens
KW - Continuous infusion
KW - FOLFOX
KW - Toxicity
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UR - http://www.scopus.com/inward/citedby.url?scp=42049112012&partnerID=8YFLogxK
U2 - 10.3816/CCC.2008.n.018
DO - 10.3816/CCC.2008.n.018
M3 - Article
C2 - 18501073
AN - SCOPUS:42049112012
SN - 1533-0028
VL - 7
SP - 134
EP - 139
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 2
ER -