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Epidemiology
Male cancer statistics
Estimated incidence Estimated deaths
Melanoma of skin 4% 3% Esophagus
Leukemia 3% 4% Leukemia
Microsatellite instability
From DeVita 6th Ed, Lipincott; H Bleiberg colorectal cancer guide, 2002, M Dunitz, and C Ribic, NEJM 2003,
Prognostic factors for colon cancer:
Stage II/III
Disease-free survival Hazard ratio p-value
Positive nodes
1–4 2.1 <0.0001
5 4.2 <0.0001
Tumour depth
T3 1.2 0.2545
T4 1.8 0.0033
High grade 1.3 0.0017
Age 60 yrs 1.0 0.6447
Female 0.94 0.4130
Right colon 0.92 0.2537
Overall survival Hazard ratio p-value
+Age 60 yrs 1.20 Significant
References in comments
Why examine the benefits of oxaliplatin
in stage II/III?: evidence from MCRC
de Gramont, 20001 Goldberg, 20042
FOLFOX LV5-FU2 FOLFOX IFL
RR
(%) 50.7* 22.3 45 †
31
PFS
(months) 8.2* 6.0 8.7 †
6.9
OS
(months) 16.2 14.7 19.5* 15.0
2
Goldberg RM, et al. J Clin Oncol 2004;22:23–30
Do
Do the benefits of oxaliplatin
oxaliplatin in
in advanced
advanced
colon
colon cancer
cancer translate
translate to
to earlier
earlier disease?
disease?
MOSAIC trial
LV5FU2 in adjuvant colon cancer
R
LV5FU2
905 patients
Median follow up 41 months
DFS similar in both arms (127 vs 124 events, p= 0.74)
(73% patients disease free at 3 y)
Deaths : 73 in LV5FU2 vs 59 in Mayo, p= 0.18
Toxicities significantly lower in the LV5FU2 (p<0.001)
André T et al. J Clin Oncol, 2003, 21, 2896 - 2903
M O S A I C
MOSAIC
Multicenter International Study of
Oxaliplatin/5FU-LV in the Adjuvant treatment of
Colon Cancer
MOSAIC: Design
R
LV5FU2
Endpoints Primary:
– Disease Free Survival (DFS)
Secondary:
– Safety (including long-term)
LV LV
LV
5-FU infusion* 5-FU infusion*
Oxali
R
D1 5-FU bolus D2 5-FU
5-FU bolus
bolus
Stratification for:
Center
Extent of invasion of the primary tumor (T2, T3, or T4)
Number of involved lymph nodes (N0, N1, N2)
Bowel obstruction or tumor perforation
Every 6 months:
Clinical examination, imaging, CEA
Diagnosis of recurrence:
- radiological recurrence on imaging
- and/or positive cytology or biopsy
B D 37 patients Cy 17 patients
135 patients
Au
133 patients S
36 patients Sg 17 patients
Gr 3 patients
107 patients Ch
2246 patients
(Oct 98-Jan 01)
André T et al. N Engl J Med 2004; 350:2343-51
MOSAIC: Patients characteristics
FOLFOX4 LV5FU2
(n=1123) (n=1123)
Bowel obstruction % 18 19
Perforation % 7 7
0.8
0.7
0.0
0 6 12 18 24 30 36 42 48 54 60 66
DFS (months) de Gramont A et al. ESMO 2004 accepted abstract
Disease-free survival: stage III patients
Median follow-up 44.2 months
Probability
3-year DFS
1.0 FOLFOX4 (n=672) 72.8%
LV5FU2 (n=675) 65.8%
0.9
HR (95% CI): 0.75 (0.62─0.90); p=0.002
25% risk reduction in the FOLFOX4 arm
0.8
0.7
0.6
0.0
0 6 12 18 24 30 36 42 48 54 60 66
DFS (months) de Gramont A et al. ESMO 2004 accepted abstract
Disease-free survival: stage II patients
Median follow-up 44.2 months
Probability
3-year DFS
1.0 FOLFOX4 (n=451) 87.4%
LV5FU2 (n=448) 84.3%
0.9
0.8
0.7
0.0
0 6 12 18 24 30 36 42 48 54 60 66
DFS (months) de Gramont A et al. ESMO 2004 accepted abstract
Analysis of DFS according to disease stage
T4
T1, T2, T3
N2
N0, N1
Stage III
Stage II
0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6
Hazard ratio and 95% CI
No of patients
Total Gr 0 (%) Gr 1 (%) Gr 2 (%) Gr 3 (%)
During 1106 87 (7.9) 533 (48.2) 349 (31.5) 137 (12.4)
treatment
1-month 1092 424 (38.8) 439 (40.2) 174 (15.9) 55 (5.0)
follow-up
6-month 1058 624 (59.0) 338 (31.9) 82 (7.7) 14 (1.3)
follow-up
12-month 1018 718 (70.5) 240 (23.6) 49 (4.8) 11 (1.1)
follow-up
18-month 967 738 (76.3) 191 (19.8) 33 (3.4) 5 (0.5)
follow-up
60 Grade 2 – mild or
moderate objective
50 sensory loss, moderate
paresthesia
40
30 Grade 3 – severe
objective sensory loss
20 or paresthesia that
interfere with function
10
0
During 1 month 6 months 12 months 18 months
treatment
Follow-up
*
André T et al. N Engl J Med 2004; 350:2343-51
Disease-free survival
versus overall survival
On an arm-by-arm basis:
3-year DFS is an excellent predictor of 5-year OS
www.mayoclinic.com/calcs/