We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy (TP-CCRT) as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma (ESCC).

We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma.

Inclusion Criteria:

1. Pathologically proven squamous cell carcinoma of esophagus.

2. Loco-regional diseases, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (6th edition) in 2002, fulfilling one of the following criteria:

   A. T3, N0, M0; B. T1-3, N1, M0; C. T1-3 or N0-1, M1a will be eligible provided the lesions could be covered by appropriate radiation fields.

3. Age ≥ 18 years old.

4. Performance status ECOG 0~2.

5. Adequate bone marrow reserves, defined as:

   A. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; B. platelets ≥ 100,000/µl.

6. Adequate liver function reserves, defined as:

   A. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); B. serum total bilirubin ≤ 1.5 x upper limit of normal (ULN).

7. Adequate renal function: Creatinine ≤1.5 mg/dl

8. Written informed consent.

Exclusion Criteria:

1. Invasion to surrounding organ (T4 disease).

2. Distant metastasis, except M1a disease listed in the inclusion criteria 2-C.

3. Adenocarcinoma of gastroesophageal (GE) junction.

4. Prior thoracic irradiation.

5. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer.

6. Prior malignancy, except for the following:

   A. adequately treated basal cell or squamous cell skin cancer; B. in-situ cervical cancer; C. Note: previously treated aerodigestive squamous cell carcinoma is not allowed.

7. Significant co-morbid disease, which prohibit the conduction of chemotherapy, concurrent chemoradiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders.

8. Estimated life expectancy less than 3 months.