The investigators hypothesize that the combination of the FOLFIRINOX regimen (a combination of 5-fluorouracil, irinotecan and oxaliplatin chemotherapy) to provide maximal systemic disease control and FDR-gemcitabine chemotherapy with concurrent IMRT (Radiation therapy) to address local disease, will achieve a significant improvement R0 resection (Radiation oncology repeat surgeries) rate in borderline resectable (surgical) pancreatic cancer and enhance disease free and overall survival in this patient population.

Gemcitabine has been the cornerstone of systemic therapy for pancreas cancer over this past decade. Recently, a combination of 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) was reported to have significant efficacy in advanced pancreatic cancer. Preclinical data suggests synergy between irinotecan and 5FU as well as between oxaliplatin and 5FU. Results of a phase II trial in advanced disease were reported in 2005 demonstrating a 26% confirmed response rate and median overall survival of 10.2 months. A follow-up phase III trial comparing FOLFIRINOX with gemcitabine for patients <75 years of age with advanced pancreatic cancer was presented at ASCO 2010 revealing improvement in PFS (6.4 vs 3.3 months, p=<.0001) and improved disease control rate (CR+PR+SD) (70.2% vs 50.9%, p=.0003). The most notable result was an impressive improvement in median overall survival with FOLFIRINOX compared to gemcitabine (11.1vs 6.8 months, p-value = <.0001, HR=.57). The main toxicity was grade 3/4 neutropenia (45.7% vs 18.7%, p=.0001) and increased risk of febrile neutropenia (5.4% vs 0.6%, p=.009)31.

Inclusion Criteria:

• Patients must have cytologic or histologic confirmation of carcinoma arising in the pancreas.
• Patients must be deemed to have borderline resectable disease with no radiologic evidence of distant metastatic disease prior to registration.
• Specifically, patients must have at least one designation of borderline resectable and no designation of unresectable disease.
• Patients must have a life expectancy of at least 12 weeks, a Zubrod performance status of < 1 and be willing and medically able to undergo surgical resection.
• Patients must have adequate organ function defined as follows: absolute neutrophil count of > 1500/mm3, platelets > 100,000/mm3, serum Cr < 1.5 mg/dl, total bilirubin < 2.0 mg/dl with relief of biliary obstruction if present (PTC tube or endobiliary stent).
• Patients must be free of other active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
• Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial due to the unacceptable teratogenic toxicity of abdominal radiation and cytotoxic chemotherapy.
• Patients must be aware of the investigational nature of the therapy and provide written informed consent.

Exclusion Criteria:

• Patients with neuroendocrine tumors are excluded.
• Active systemic malignancy, ongoing infection, or any other serious uncontrolled, concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
• Patients with preexisting peripheral neuropathy > grade 2 are ineligible
• Pregnant or nursing women are ineligible.
• Patients must have no history of previous chemotherapy for pancreatic cancer or any abdominal radiation therapy.
• Patients may not have used any investigational agent within 4 weeks prior to enrollment into the study.

30 days post treatment