The purpose of this study is to see whether giving azacitidine before each cycle of chemotherapy prior to surgery is safe.

Currently patients with resectable (can be removed by surgery) esophageal cancer will receive chemotherapy before surgery to try to shrink the tumor before it is removed. This study will evaluate whether giving azacitidine before each cycle of chemotherapy to increase the shrinkage of the tumor prior to surgery is safe.

Azacitidine is currently approved by the Food and Drug Administration (FDA) for treatment of myelodysplastic syndrome (MDS). Azacitidine is not approved by the FDA for use in this study and is therefore considered investigational. Because azacitidine has not been given before in combination with epirubicin, oxaliplatin and capecitabine, we will also evaluate the safety and tolerability of azacitidine and find out what dose of azacitidine is safe to give with this chemotherapy.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus or gastroesophageal junction (GEJ) and deemed resectable by the thoracic surgeon.
• No prior chemotherapy for esophageal or GEJ cancer.
• ECOG Performance status 0-2.
• Adequate bone marrow, kidney and liver function.
• Ability to understand and the willingness to sign a written informed consent document.
• Subjects of child-bearing potential must agree to use effective means of contraception (men and women).
• Prior malignancy is acceptable if the subject is considered to be cured. In most cases this will mean a 5-year disease-free period.

Exclusion Criteria:

• Patients with cervical esophageal cancer or esophageal cancer with squamous cell carcinoma morphology.
• Subjects receiving any other investigational agent or received prior chemotherapy for esophageal or GEJ cancer.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, epirubicin, oxaliplatin, capecitabine and mannitol.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
• Pregnant (positive pregnancy test) or lactating women.
• Patients with active infection, serious inter-current medical conditions.