1. Surgery of colorectal metastasis in the Optimox 1 study. A GERCOR Study.
N. Perez-Staub, G. Lledo, F. Paye, B. Gayet, M. Flesch, A. Cervantes, A. Figer, O. Bourges, T. André, A. de Gramont
GERCOR Paris, France.

2. Abstract
Background: Surgery of metastasis can cure approximately 20% of metastatic colorectal cancer (MCRC) patients. The Optimox 1 study achieved a response rate over 50% with FOLFOX therapy in patients (pts) with initially unresectable metastasis which allowed to perform surgery in a significant number of pts (JCO 2006). We report here the results in pts who underwent surgery of metastasis (met).
Methods: From jan 2000 to june 2002, 620 previously untreated patients with unresectable metastasis were randomized between FOLFOX4 every two weeks until progression (arm A), or FOLFOX7 for 6 cycles, maintenance without oxaliplatin for 12 cycles and reintroduction of FOLFOX7 (arm B). 98 pts (15.8%) were resected with a curative intent, 54 in arm A and 44 in arm B.
Results: Patients characteristics were (arm A/B %): metachronous metastasis 19/23, liver met 85/93, lung met 20/20, other met 7/2, PAL < 3 ULN: 98/98, normal LDH: 51/50. 9% of pts achieved a complete response, 72.5% a partial response, 17% a stable disease. 86 pts had a single resection, 12 had a two-stage surgery. Four patients died in arm B. Fourteen pts who relapsed had a second surgery. Resection was radical (R0) for 72 pts (43 in arm A and 29 in arm B), 13 were R1 (margin invasion) and 12 were R2. R0/R1 patients had a median overall survival (OS) of 51 mo in arm A and 38 mo in arm B. Median disease-free survival (DFS) since surgery was 12 mo in arm A and 9 mo in arm B, with no statistical difference. 32% of R0/R1 pts were alive with no progression at 3 years in arm A and 20% in arm B. Median time from randomization to surgery was 8 mo. No difference was found between patients resected before 8 mo (n = 50) and after (n = 37) in OS (39 vs 45 mo, p = .67) nor in DFS (11.6 vs 9.5 mo, p = .24). Neither in pts resected before and after 6 mo in OS (p=.77) and DFS (p = .44).
Conclusion: FOLFOX treatment allowed 14 % of unresectable patients to have R0 or R1 surgery of their metastases. There was no additional benefit to perform surgery after 6 months of therapy compared to early surgery.

3. INTRODUCTION
Oxaliplatin-based chemotherapy induction strategy enable % of liver colorectal metastatic patients to be secondarly resected (Adam et al, Ann Surg 2004).
Long term survival can be reached with a % year survival rate for these patients (Adam et al, Ann Surg 2004).
5-year survival rate for patients with extra hepatic disease who can be resected is also 35%
98 patients initialy unresectable were resected with curative intent in the Optimox 1 study (Tournigand et al, JCO 2006).

4. Patients and Methods Inclusion criteria Optimox 1 study design
Histologically proven colorectal cancer
Unresectable metastases
No prior CT except adjuvant CT if ended  6 months before study entry
WHO PS  2
Adequate hematological, renal and liver functions
< 80 years
Evaluation after 4, 6 and then every 6 cycles

5. Optimox 1 surgery Patients Characteristics
Folfox4 N = 54
Folfox7 N = 44
All N= 98 (%)
Age [ ] [ ] [ ]
Male/Female / / / (49/51)
WHO PS 0/ / / / (72/28)
Colon/Rectum/both /15/ /17/ /32/1 (66/33/1)
Adjuvant CT (15)
Ph Alk ≤ 3/ > 3 UNL / / / (98/2)
LDH N/ >UNL/uk /16/ /14/ /30/18 (52/30/18)
CEA
- N (36)
- < 10 UNL (36)
- 10 – 100 UNL (19)
- > 100 UNL (8)
- uk (1)

6. Optimox 1 Surgery: Metastases at diagnosis
Folfox4 N=54
Folfox7 N=44
All N= 98 (%)
Synchro/Metachronous / /10/1uk /20 (78,5/20)
Nb of metastatic sites 1/ ≥ / / /16 (84/16)
Metastases location
Liver (89)
Lung (20)
Other: peritoneum/ (5)
ovary/ lymph nodes
Median size (mm) [5- 176] [ ] [ ]

7. Optimox 1 Surgery Response rate, delay, cycles number
Folfox4
N = 54
Folfox7
N = 44
All
N = 98 (%)
Complete Response 4 5
9 (9%)
Partial Response 39 32
71 (72.5%)
Stable Disease 10 7
17 (17.5%)
Progressive Disease 1
0 (1%)
Median delay chemo-surg. 8 9
8.0 months
N cycles [range]
12 [4 - 23]
13 [5 - 25]
12 [4 - 25]
Median follow-up 30.8 months

8. Optimox 1 surgery Surgery characteristics (2)
Folfox4 N = 54
Folfox7 N = 44
All N = 98 (%)
One stage surgery / 1NA (87/1)
Two stages surgery (12)
New surgery after progression
- 2nd (14)
- 3rd (3)
Resection
- R (73,5)
- R (13)
- R (12)
- NA hepatocarcinoma
Post operative mortality (4)
3 patients died after third surgery

9. Optimox 1 Surgery: Disease-free survival since R0-R1 surgery

10. Optimox 1 Surgery: Overall Survival since R0-R1 surgery

11. Optimox 1 Surgery: OS according to time to surgery

12. Optimox 1 Surgery: DFS according to time to surgery

13. Optimox 1 Surgery Conclusion