RATIONALE: Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to kill tumor cells or stop them from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with panitumumab and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving panitumumab together with docetaxel, cisplatin, radiation therapy, and surgery works in treating patients with newly diagnosed, locally advanced esophageal cancer or cancer of the gastroesophageal junction.

OBJECTIVES:

Primary

• To determine the pathologic complete response rate in patients with newly diagnosed, locally advanced adenocarcinoma of the distal esophagus or gastroesophageal junction treated with neoadjuvant panitumumab and combination chemoradiotherapy followed by surgery.

Secondary

• To determine the near-complete pathologic response rate in the primary tumor (≤ 10% residual viable cancer).
• To determine the overall survival and disease-free survival rates of these patients.
• To determine the safety profile of this regimen.

OUTLINE: Patients receive panitumumab IV over 1 hour, docetaxel IV over 1 hour, and cisplatin IV over 1-2 hours on day 1 in weeks 1, 3, 5, 7, and 9. Patients also undergo radiotherapy once daily 5 days a week beginning in week 5 and continuing for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-9 weeks after completion of chemoradiotherapy, patients with no evidence of metastatic disease undergo esophagectomy.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year OR every 6 months for 3 years.

1. ≥ 18 years old

2. ECOG/Zubrod Performance Status 0-1

3. Biopsy-proven resectable primary (nonrecurrent) adenocarcinoma of the distal esophagus or GE junction (Siewert Type I or II)

   • Siewert Type I: adenocarcinoma of the distal esophagus
   • Siewert Type II: adenocarcinoma of the esophago-gastric junction/real cardia

4. Pre-registration EUS, CT of chest and upper abdomen, and PET must support a clinical stage of T3N0M0, T2-3N1M0 or T2-3N0-1M1a (celiac adenopathy must be ≤ 2 cm by EUS). Clinically staged T1 tumors and T2N0M0 tumors are not eligible. N1 does not require biopsy/FNA. Note: Patients requiring a stent for nutrition must have staging examinations and scans completed before stent placement.

5. No definitive radiological evidence of distant metastases.

6. No pre-existing grade 2 or greater peripheral neuropathy (CTCAE v3) of any etiology.

7. Adequate bone marrow, hepatic and renal function prior to registration:

   • WBC ≥ 3,000/mm³
   • ANC ≥ 1,500/mm³
   • Platelet count ≥ 100,000/mm³
   • Hemoglobin ≥ 9.5 g/dL
   • Creatinine ≤ 1.5 mg/dL
   • Total bilirubin ≤ 3 mg/dL
   • AST (SGOT) ≤ 2.0 times upper limit of normal (ULN)
   • ALT (SGPT) ≤ 2.0 times ULN
   • Alkaline phosphatase ≤ 2.0 times ULN
   • Albumin ≥ 2.0 g/dL OR prealbumin ≥ 15 mg/dL
   • Magnesium ≥ lower limit of normal (LLN)

8. Patient must be evaluated before registration by medical oncologist, radiation oncologist and surgeon and deemed fit for protocol therapy and surgery.

9. No prior invasive malignancy, unless disease-free for ≥ 5 years prior to registration (Exceptions: non-melanoma skin cancer, in-situ cancers).

10. Non-pregnant and non-breast feeding. Female participants of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic ≥ 12 months to be considered not of childbearing potential. All patients of reproductive potential must agree to use an an effective method of birth-control while receiving study therapy and for six months after completion of therapy.

11. No prior chest or upper abdomen radiotherapy; prior therapy with cisplatin, docetaxel, panitumumab or other anti-EGFR therapy or prior esophageal or gastric surgery (Exception: prior surgery to treat reflux disease)

12. No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psyschiatric illness/social situations that would limit compliance with study requirements.

13. No history of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan

14. No history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.