A consistent finding in many studies in patients with operable esophageal and gastro-esophageal junction (GEJ) cancer is that response to preoperative therapy, particularly the absence of residual disease in the surgical specimen, is an indicator of better disease-free and overall survival. Therefore in the investigators trial the investigators will evaluate the pathologic response of panitumumab in combination with neoadjuvant chemoradiation as first line treatment of operable adenocarcinomas, undifferentiated or squamous cell carcinomas of the esophagus.

This is a Phase II, non-randomized trial. Eligible subjects will be treated with panitumumab plus carboplatin, paclitaxel and radiotherapy followed by surgical resection of the esophagus.

Panitumumab administration schedule: Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, prior to administration of chemotherapy at a dose of 6 mg/kg on day 1, 15 and 29. If the first infusion is well tolerated (without any serious infusion related reactions) all subsequent infusions may be administered over 30 minutes ± 10 minutes.

Chemotherapy regimen: Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29. Both drugs will be infused over one hour.

Radiotherapy treatment: A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy. All patients will be radiated by external beam radiation, using 3-D conformal radiation technique.

Surgery: Surgery will be performed preferably within 6 weeks after the completion of the chemoradiation and panitumumab. For carcinomas distal of the tracheal bifurcation but proximal to the gastro-esophageal junction, a transthoracic approach is preferred. For distal tumors involving the gastro-esophageal junction a transhiatal esophageal resection is preferred. A wide local excision including the N1 lymph nodes is carried out in both techniques including a standard excision of the lymph nodes around the coeliac axis. The continuity of the digestive tract will be restored by a gastric tube reconstruction or colonic interposition procedure with an anastomosis in the neck.

Inclusion Criteria:

• Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the intrathoracic esophagus or gastro esophageal junction
• Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen.
• T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible
• Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm
• If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach. Gastric cancers with minor involvement of the GE junction or distal esophagus are not eligible
• No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula
• Non pregnant, non-lactating female patients, not planning to become pregnant within 6 months after the end of treatment.
• Age ≥ 18 and ≤ 75
• ECOG performance status 0 or 1
• Adequate hematological, renal, hepatic and pulmonary functions
• Written, voluntary informed consent
• Patients must be accessible to follow up and management in the treatment center

Exclusion Criteria:

• Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment
• Pregnancy (positive serum pregnancy test) and lactation
• Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment
• Previous chemotherapy, radiotherapy, treatment with an anti-EGFR antibody or with small molecule EGFR inhibitors
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization
• Pulmonary fibrosis
• Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
• Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.
• Dementia or altered mental status that would prohibit the understanding and giving of informed consent
• Inadequate caloric- and/or fluid intake
• Weight loss > 15%.