The primary objective of this study is to evaluate the efficacy of PG2 concurrent with concurrent chemoradiation therapy (CCRT) for relieving fatigue among locally advanced esophageal cancer patients who are under preoperative chemoradiation therapy at curative setting. This study will be designed to compare the fatigue status between two study arms patients under CCRT.

The secondary objective is to assess the efficacy of PG2 to improve the quality of life of patient during CCRT. Also, the investigators try to determine the effect of PG2 on tumor response post CCRT, disease free survival (DFS) and overall survival (OS) of patients by comparing the above outcome between the two study arms.

The mechanism of immunomodulatory of PG2 and tumor response, DFS and OS for patients with esophageal cancer treated with preoperative CCRT concurrent with or without PG2 will be investigated in add-on study.

It's randomized, open-label study. Locally advanced esophageal cancer patients who give consent to participate in this study and meet all other inclusion and exclusion criteria will be eligible to enroll into this study. The eligible patients will be randomized into one of two study arms: 1) the CCRT- PG2 arm; and 2) the CCRT alone arm. All eligible patients will receive the standard preoperative CCRT during study period and standard surgery 6 weeks after completion of radiation therapy.

The primary objective of this study is to evaluate the efficacy of PG2 concurrent with CCRT for relieving fatigue. Patient's fatigue status will be measured by the BFI-T.

The secondary objective is to assess the efficacy of PG2 to improve the quality of life of patient during CCRT. Patients' quality of life will be assessed by the Functional Assessment of Cancer Therapy- General (FACT-G7 v.4). Patients' appetite will be assessed by VAS appetite score. The effect of PG2 on tumor response post CCRT, DFS and OS of patients will also be evaluated.

Peripheral blood samples and tumor biopsy samples will be collected from all subjects at screening period, during CCRT and post CCRT period to perform Immune biomarker assessment in the add-on study.

Inclusion Criteria:

• Patients who signed the informed consent form;
• The age of eligible patients should be 20-75 years old;
• Performance status of ECOG 0-1 at time of screening;
• Have Esophageal and esophagogastric junction cancer (non-cervical esophagus);
• Have stage IIB-IIIB locally advanced carcinoma of esophagus;
• Pathologically confirmed primary squamous cell carcinoma of the esophagus;
• Patient must be willing and able to complete fatigue and quality of life questionnaires.

Exclusion Criteria:

• BFI > 7 at time of screening;
• Concomitant malignancy or prior invasive malignancy unless disease free for a minimum of 2 years;
• Medical contraindications to esophagectomy;
• Female patients are pregnant or breast-feeding;
• Have inadequate bone marrow, liver, and renal function
• Uncontrolled systemic disease
• Regular steroid use as determined by investigators;
• Patients take central nervous system stimulators such as Methylphenidate within 30 days before screening;
• Patients have enrolled or have not yet completed other investigational drug trials within 30 days before screening.
• BMI < 16
• Nutrition status SGA rating C.