Reviewer: Dr Phil Bedard

1
Oxaliplatin/5FU/LV in adjuvant colon cancer
Updated efficacy results of the MOSAIC trial,
including survival, with a median follow-up of
six years Authors Gramont et al.

• Reviewer Dr Phil Bedard
• Date posted June 21, 2007

2
Background

• MOSAIC trial
• Primary endpoint DFS
• Advantage in 3-yr and 5-yr DFS for FOLFOX4
  compared with LV5FU2 in Stage II or III colon
  cancer
• Secondary endpoint OS, safety

3
Study Design
FOLFOX4 Leucovorin 200mg/m2 IV over 2 hours 5-FU
400mg/m2 IV over 2 hours, then 600mg/m2
continuous IV infusion over 22 hours days 1 and
2 Oxaliplatin 85mg/m2 IV N1123
Patients with resected Stage II or Stage III
colon cancer N2246
LV5FU2 Leucovorin 200mg/m2 IV over 2 hours 5-FU
400mg/m2 IV over 2 hours, then 600mg/m2
continuous IV infusion over 22 hours days 1 and
2 N1123
4
Results 6-yr OS
FOLFOX4 LV5FU2 HR p-value
Overall 78.6 76.0 0.85 (0.72-1.01) 0.057
Stage II 86.8 86.9 1.00 (0.72-1.41) 0.996
High Risk Stage II Not presented Not Presented 0.93 (0.6 -1.4) (estimated from graph presented)
Stage III 73.0 68.6 0.80 (0.66-0.98) 0.029
High-risk stage II- defined as at least one of
the following T4, tumor perforation, bowel
obstruction, poorly differentiated tumor, venous
invasion , lt10 lymph nodes examined 5 Yr DFS HR
0.74 (0.52-1.06) 5 yr DFS 82.1 (FOLFOX 4 vs
74.9 LV5FU2)
5
Results

• Incidence of peripheral neuropathy at 4 years in
  FOLFOX 4 arm
• Grade 1 12.0
• Grade 2 2.8
• Grade 3 0.7

6
Study Commentary

• There is an OS benefit for Stage III patients
  with FOLFOX4
• DFS but no OS survival benefit in high risk stage
  II patients
• There may not have been power to detect a
  survival benefit in this subset of patients
• ? Meta analysis possible with patients from NSABP
  C07
• Although there is evidence of recovery from
  peripheral neuropathy,
• 15 of patients had neuropathy at 4 years
• lt 1 have grade 3 neuropathy at 4 yrs

7
Bottom Line for Canadian Medical Oncologists

• Adjuvant FOLFOX4 improves DFS and OS in resected
  stage III colon cancer
• ? Role of FOLFOX4 in high risk stage II
• There is no role for FOLFOX4 in low-risk stage II
  colon cancer
• Patients should be warned about the risk of
  persistent neuropathy with oxaliplatin