The pancreas cancer is the 4th cause of death. All stage confused, the survival at 5 years is note over 5 %. At metastatic stage, the pancreatic adenocarcinoma is an incurable disease with the survival median of 2-4 months without chemotherapy.

Up to 2011, gemcitabine was the only reference treatment of this type of cancer. But until, the FOLFIRINOX could permitted to improve significantly the overall survival (6,8 months with gemcitabine vs 11,1 months with FOLFIRINOX) and the progression free survival (3,3 months with gemcitabine vs 6,4 months with FOLFIRINOX) for patients under 76 years. Main toxicities of this treatment are hematological, gastrointestinal and neuropathy with apparition of sensitive neuropathy, reversible, related to oxaliplatin.

These results are on a population under 76 years old. In this study, the median age of patients at inclusion was 61 years old and FOLFIRINOX was still beneficial for patients more than 65 years old. Given the increase of proportion of patients than more of 65 years old with pancreatic cancer and given the increase of life expected, it is important to know the effectiveness and tolerance of such treatment for patient older than 65 years and 76 years.

FIRGEM is an original strategic sequential treatment witch alternates, every 2 month, 4 cycles of FOLFIRI.3 and 2 cycles of 3 injections of gemcitabine. There is no cross resistance known between this 2 treatments witch limit toxicities and preserve quality of life of patients. A Phase II trial testing this treatment regimen to classical regimen of gemecitabine, showed an overall survival of 11 months in the FIRGEM regimen and an overall survival of 8,2 months in the gemcitabine regimen. The rate of progression was 45% near of progression rate with FOLFIRINOX. Tolerance is close to that FOLFIRINOX regimen but this strategic doesn't induce limiting neurotoxicities and allow to use oxaliplatin in 2de line of treatment.

The trial propose to evaluate the effectiveness and tolerance of FOLFIRINOX regimen (8 cycles) with LV5FU2 in maintenance (that could increase the FOLFIRINOX tolerable without decrease efficiency), to FIRGEM regimen and to FOLFIRINOX (12 cycles) which is the reference regimen.

Inclusion Criteria:

• Metastatic disease
• At least one mesurable lesion according to RECIST V1.1 criteria
• No prior chemotherapy (excepted if there is at least on lestion out of the irradition area)
• Age > 18 years. A favorable adviced by an onco geriatrician would be mandatory for inclusion of patients older than 75 older
• Performance statut (WHO) 0-1
• Polynyclear ≥ 1500/mm3
• Bilirubine ≤ 1,5 fois la LSN, creatinin < 120μmol / L
• Signed informed consent form

Exclusion Criteria:

• Another type of pancreas tumor, as endocrine tumor ou with acinous cells
• Ampulloma
• Cerebral or meningeal metastasis
• Gilbert disease
• Neuropathie > or = grade 1
• Study treatments contraindication
• Uncontrolled diarrhoea or inflamatory disease of colon or rectum, or bowel obstruction or bowel sub-obstruction no resolved with specific treatment
• Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease prevent patient to receive study Cancer within the 5 years before inclusion, except for int situ cancer of the neck of the uterus or basal cell skin cancer
• Significant previous cardiac and respiratory disease
• Patient included in an other therapeutic study with experimental treatment
• Pregnancy or breast feeding
• Patient depreved of freedom or under gardianship
• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule