FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

Inclusion Criteria: * Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, GEJ, or GC based on biopsy material or adequate cytologic exam; tumors of the GC are defined as originating within 5 cm of the GEJ * Patients must be clinically staged according to the 7th edition (2010) of the American Joint Committee on Cancer (AJCC) staging system and must have either clinical T3-4a, or ≥ N1 disease; staging should include upper endoscopy with endoscopic ultrasound and a fludeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan (with diagnostic CT abdomen/pelvis preferred) * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Absolute neutrophil count ≥ 1,500/ul * Platelet count ≥100,000/ul * Serum creatinine (Scr) ≤ 1.5mg/dl; if the Scr \> 1.5, patients may still be eligible if the calculated glomerular filtration rate (GFR) (Cockroft-Gault) is ≥ 40ml/minute * Serum total bilirubin ≤ 1.5X the institutional upper limit of normal (ULN) * Alkaline phosphatase ≤ 3X the institutional ULN * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3X the institutional ULN * Patients with Gilbert's syndrome are eligible provided the total bilirubin is ≤ 3 and the remainder of the liver function tests (ALT, AST, alkaline phosphatase \[ALK Phos\]) are within the institutional normal range * Patients must have a forced expiratory volume in one second (FEV-1) and diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% predicted * Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial * Patients of childbearing potential must agree to use an effective form of contraception during this study and for 90 days following the last dose of chemotherapy; an effective form of contraception is an oral contraceptive or a double barrier method Exclusion Criteria: * Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma, etc.) will be ineligible * Patients with evidence of clinical T4b (unresectable) or M1 (distant metastasis) according to the AJCC 2010 staging system will be ineligible * No prior chemotherapy, radiation therapy, or surgery for this malignancy will be allowed; prior endoscopic procedures for superficial disease (endoscopic mucosal resection, cryotherapy, photodynamic therapy, etc.) will not exclude a patient; prior dilatation is also allowed * Patients with another active malignancy will not be eligible except for: * Resected basal cell carcinoma and squamous cell carcinoma of the skin, cervical or prostatic intraepithelial neoplasia, and ductal or lobular carcinoma in situ of the breast * Patients with localized prostate cancer who have received curative intent therapy are also eligible provided: * Surgically treated patients have an undetectable prostate specific antigen (PSA) * Patients treated with brachytherapy have a PSA within the institutional normal range * Patients who have received pelvic external beam radiotherapy are not eligible * Patients with a clinically apparent active infection will not be eligible (please note, an isolated elevation in the white blood cell count, by itself, does not constitute evidence of an infection) * Patients with known hypersensitivity to any component of the chemotherapy regimen will not be eligible * Patients with a baseline peripheral neuropathy ≥ grade 2 will not be eligible * Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy as defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible * Patients who are pregnant or lactating will not be eligible; pregnant patients are ineligible * Patients with angina, a cardiac ejection fraction \< 50%, or ischemic heart disease are not eligible * Patients with any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible * Patients with any history of solid organ or bone marrow transplant will not be eligible * Patients with a known history of infection with hepatitis B or hepatitis C virus (active, previously treated, or both) will not be eligible due to the increased risk of hepatotoxicity and viral reactivation associated with systemic chemotherapy * Patients with known infection with human immunodeficiency virus (HIV) will not be eligible