| Final results of a phase III trial of 5-FU/leucovorin versus oxaliplatin versus the combination in patients with metastatic colorectal cancer following irinotecan, 5-FU, and leucovorin
Category:
Lower Gastrointestinal Cancer
Authors:
M. L. Rothenberg, A. M. Oza, B. Burger, J. Berlin, J. L. Marshall,
R. K. Ramanathan, L. L. Hart, S. Gupta, C. A. Garay, D. G. Haller,
on behalf of EFC 4584 Investigators; Vanderbilt-Ingram Cancer Ctr,
Nashville, TN; Princess Margaret Hospital, Toronto, ON, Canada;
Sanofi-Synthelabo Research, Malvern, PA; Lombardi Cancer Center,
Washington, DC; University of Pittsburgh, Pittsburgh, PA; Florida
Cancer Specialists, Ft. Myers, FL; University of Pennsylvania, Philadelphia,
PA
Abstract: In North
America, no effective therapy has been available for pts with metastatic
colorectal cancer (CRC) following irinotecan and bolus 5-FU/LV (IFL).
EFC 4584 randomized pts with progressive CRC to bolus and infusional
5-FU/LV (LV5FU2) vs. single agent oxaliplatin (OXALI) vs. the combination
(FOLFOX4) consisting of oxali 85 mg/m2 d 1 + LV 200 mg/m2,
5-FU 400 mg/m2 bolus + 600 mg/m2 as a 22 hour
infusion d 1,2 q 2 wks. From 11/00 - 2/02, 821 pts were enrolled
in this Phase III study. Median age: 59. M/F: 58%/43%. Disease in
≥ 2 organs: 72%. LDH > 1.5x NL: 42%. KPS ≤ 90: 67%. An interim
analysis of the first 463 pts demonstrated that, compared to the
control arm of LV5FU2, FOLFOX4 produced a higher RR (9.9% vs 0%,
p <.0001), longer TTP (4.6 vs 2.7 months, p <.0001), and a
higher rate of relief from tumor-related symptoms (33% vs 12%, p
<.001) (Rothenberg et al: Ann Oncol 13(Supp 5):2,2002). Safety
analysis in 789 assessable pts: (table) Final efficacy analysis
can commence after 393 deaths have occurred on the LV5FU2 and FOLFOX4
arms (~ Jan, 2003). Final intent-to-treat analysis on ~817 patients
for efficacy, which will include a comparison of overall survival
and time-to-tumor symptom worsening, will be performed in Mar, 2003
with the results available for presentation. This study was sponsored
by Sanofi-Syntheélabo.
% Of Pts With Grade 3/4 Tox
| Toxicity |
LV5FU2 |
OXALI |
FOLFOX4 |
| 　 |
N = 256 |
N = 266 |
N = 267 |
| Neutropenia |
4 / 3 |
0 / 0 |
27 / 20 |
| Neutropenic Fever |
1 / 0 |
0 / 0 |
5 / 0 |
| Thrombocytopenia |
0 / 0 |
2 / 0 |
5 / 1 |
| Nausea |
4 / - |
5 / - |
10 / - |
| Vomiting |
2 / 0 |
5 / 0 |
8 / 1 |
| Diarrhea |
2 / 0 |
4 / 0 |
12 / 1 |
| Acute Cold-Sensitive Neuropathy |
0 / 0 |
6 / 0 |
6 / 0 |
| Cumulative Neuropathy |
0 / 0 |
3 / 0 |
4 / 0 |
| Thromboembolism |
2 / 1 |
0 / 0 |
4 / 2 |
| Death Within 1st 60 Days Not Due to PD |
2 |
2 |
2 |
|
