Induction Chemotherapy for Locally Advanced Esophageal Cancer

The goal of the study is to evaluate mFOLFOX6 (5-Fluorouracil, Leucovorin and Oxaliplatin)
chemotherapy as induction treatment prior to standard neoadjuvant chemoradiation to decrease
the rate of distant recurrence among patients with locally advanced esophageal cancer.
mFOLFOX6 is frequently used to treat metastatic esophageal cancer because of its high
response rate in this setting. It has shown promising efficacy in several trials of patients
with advanced esophageal cancer and it is the most commonly used combination regimen for this
group of patients in the United States.

The investigators propose treating a sample of 40 patients with 3 cycles of induction
mFOLFOX6 chemotherapy over six weeks followed by standard chemoradiation and surgery. The
investigators hypothesize that patients who undergo induction chemotherapy with mFOLFOX6
prior to standard neoadjuvant chemoradiation and surgery will have a lower rate of distant
disease recurrence compared to standard neoadjuvant chemoradiation and surgery.

Inclusion Criteria:

1. Must have histologically proven adenocarcinoma, squamous cell carcinoma or
undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia.

2. Must have potentially resectable disease.

3. Must have ECOG performance status 0 or 1.

4. Must have adequate organ function as defined by the following criteria:

- ANC ≥ 1,500/mm3

- Platelet count ≥ 100,000/mm3

- Creatinine (Cr) ≤ 1.5 mg and/or creatinine clearance ≥ 60cc/min.

- Total bilirubin must be ≤ 1.5 x ULN unless the patient has a chronic grade 1
bilirubin elevation due to Gilbert's disease or similar syndrome due to slow
conjugation of bilirubin.

- Alkaline phosphatase must be ≤ 2 x ULN.

- AST & ALT must be ≤ 3 x ULN.

5. Men and women of reproductive potential must agree to use an effective contraception
method

6. Must be willing and able to provide written informed consent

7. Must be ≥ 18 years or older

Exclusion Criteria:

1. Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an
esophageal tumor.

2. Known distant metastases.

3. Patients with prior malignancies are eligible if they have been disease-free for > 5
years and are deemed by their physician to be at low risk for recurrence. Patients
with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ
of the cervix, or carcinoma in situ of the colon or rectum that have been effectively
treated are eligible, even if these conditions were diagnosed within 5 years prior to
randomization.

4. Known ≥ grade 2 neuropathy.

5. Known non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
preclude any of the study therapy drugs.

6. Known psychiatric or addictive disorders or other conditions that, in the opinion of
the investigator, would preclude them from meeting the study requirements.

7. Women who are pregnant or nursing.

8. Women and men of reproductive potential who are expecting to conceive or father
children.