Adjuvant Colon Cancer Trial: Design & Efficacy
Eloxatin, used in combination with infusional 5-FU/LV, is indicated for adjuvant
treatment of stage III colon cancer patients who have undergone complete
resection of the primary tumor. The indication is based on an improvement in
disease-free survival, with no demonstrated benefit in overall survival after a
median follow-up of 4 years.
Study objectives
To compare efficacy and safety as adjuvant therapy of
-
Eloxatin + infusional 5-FU/LV (FOLFOX4)
-
Infusional 5-FU/LV alone
In 2,246 patients with stage II or III colon cancer following complete resection
of the primary tumor
Primary end point
-
Disease-free survival (DFS)
Secondary end points
-
Safety
-
Overall survival (OS)
Patient characteristics
Patient characteristics were well balanced between treatment arms1
|
Sex
|
|
|
|
Male (%)
|
56.1
|
52.4
|
|
Female (%)
|
43.9
|
47.6
|
|
Median age (y)
|
61.0
|
60.0
|
|
<65 years of age (%) |
64.4
|
66.2
|
|
>65 years of age (%)
|
35.6
|
33.8
|
|
Karnofsky performance status (KPS)* (%)
|
|
|
|
100
|
29.7
|
30.5
|
|
90
|
52.2
|
53.9
|
|
80
|
4.4
|
3.3
|
|
70
|
13.2
|
11.9
|
|
<60
|
0.6
|
0.4
|
|
Primary site (%)
|
|
|
|
Colon including cecum
|
54.6
|
54.4
|
|
Sigmoid
|
31.9
|
33.8
|
|
Rectosigmoid
|
12.9
|
10.9
|
|
Other, including rectum
|
0.6
|
0.9
|
|
Bowel obstruction (%)
|
|
|
|
Yes
|
17.9
|
19.3
|
|
Perforation (%)
|
|
|
|
Yes
|
6.9
|
6.9
|
|
Stage at randomization (%)
|
|
|
|
II (T=3,4, N=0, M=0)
|
40.1
|
39.9
|
|
III (T=any, N=1,2, M=0) |
59.6
|
59.3
|
|
IV (T=any, N=any, M=1) |
0.4
|
0.8
|
|
Staging - T (%)
|
|
|
|
T1
|
0.5
|
0.7
|
|
T2
|
4.5
|
4.8
|
|
T3
|
76.0
|
75.9
|
|
T4
|
19.0
|
18.5
|
|
Staging - N (%)
|
|
|
|
N0
|
40.2
|
39.9
|
|
N1
|
39.4
|
39.4
|
|
N2
|
20.4
|
20.7
|
|
Staging - M (%)
|
|
|
|
M1
|
0.4
|
0.8
|
*KPS relation to ECOG score:
KPS 100 = ECOG 0
KPS 80-90 = ECOG 1
KPS 60-70 = ECOG 2.
Approximately 85% of patients were ECOG 0-1
Efficacy outcomes
In adjuvant therapy for stage III colon cancer, Eloxatin + infusional 5-FU/LV is the first regimen to demonstrate
significant reduction in the risk of recurrence vs infusional 5-FU/LV alone
-
DFS curves diverged as early as 6 months, with the separation continuing
throughout follow-up
-
Endorsed by Oncologic Drugs Advisory Committee (ODAC) as an appropriate end
point in this setting and a basis for FDA full approval2
-
3-year DFS is an excellent predictor of 5-year OS based on meta-analyses of
adjuvant colon cancer trials3
References:
-
Eloxatin® (oxaliplatin injection) prescribing information, sanofi-aventis.
-
U.S. Food and Drug Administration Oncologic Drugs Advisory
Committee. Meeting transcript, Tuesday, May 4, 2004. Available at:
http://www.fda.gov/ohrms/dockets/ac/04/transcripts/4037T2.htm.
Accessed September 7, 2004.
-
Sargent DJ, Wieand HS, DG Haller, et al. Disease-free survival
vs. overall survival as a primary endpoint for adjuvant colon cancer studies:
individual patient data from 20.898 patients on 18 randomized trials. J Clin
Oncol 2005; 23:8664-8670.