Neoadjuvant Chemotherapy Versus Surgery Alone for Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The effect of neo-adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains the most controversial part of neo-adjuvant therapy for esophageal carcinomas. One of our objectives is to evaluate whether the neo-adjuvant therapy with cisplatin and paclitaxel followed by right thoracic approach esophagectomy with total 2-field lymph node dissection improves the overall survival of thoracic esophageal cancer patients.

Detailed Description
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The effect of Neo-adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains the most controversial part of Neo-adjuvant therapy for esophageal carcinomas. Therefore, the optimal management of resectable esophageal squamous cell carcinomas differs widely among different areas based on local randomized controlled trials. The neo-adjuvant chemotherapy might be a good strategy if sufficient local control is achieved by surgical treatment. This study defined the detail of surgery procedure and the region of lymphadenectomy and adopted cisplatin and paclitaxel as neoadjuvant chemotherapy regimens. We try to evaluate the efficacy and safety of this neo-adjuvant strategy.

Official Title
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A Phase III, Multicenter Randomized Controlled Study of Neo-adjuvant Chemotherapy Paclitaxel + Cisplatin Versus Surgery Alone for Stage IIA-IIIB Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Neoplasm

Intervention / Treatment
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* Drug: cisplatin and paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage IIA to IIIB, (7th Union for International Cancer Control, UICC-TNM). Patients must not have received any prior anticancer therapy of esophageal carcinoma. Age ranges from 18 to 75 years. Without operative contraindication. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney, total bilirubin（TBIL）≤1.5N, aspartate aminotransferase (AST)≤2.5N, alanine aminotransferase(ALT)≤2.5N, prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range, endogenous creatinine clearance rate(CRE)≤1.5N. Patients must not have diagnosed with other cancer and must not received any prior anticancer therapy except prostatic cancer with more than 5 years disease-free survival(DFS). expected R0 resection. ECOG 0～2. Signed informed consent document on file. 10.No metastatic lymph node in cervical by color doppler sonography. Exclusion Criteria: Multiple primary cancer. The subject cannot understand and sign the informed consent form(ICF). Patients with concomitant hemorrhagic disease. Any un expected reason for patients can't get operation. Inability to use gastric conduit after esophagectomy because of a prior surgery. Pregnant or breast feeding. Patients are diagnosed or suspected to be allergic to cisplatin or Paclitaxel.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neo-adjuvant chemotherapy group<br>Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles. Paclitaxel, 87.5mg/m2, d1,d8, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles. Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). | Drug: cisplatin and paclitaxel<br>* Paclitaxel, 175mg/m2, d1, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles. Paclitaxel, 87.5mg/m2, d1,d8, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles. Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles.<br>* Other names: TP;|
| No Intervention: Surgery alone group<br>Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate |  | 1 years and 3 years | 
| Disease free survival |  | 5 years | 
| assessment in perioperation-Removal rate (R0 resection rate) | The R0 resection rate of two groups | perioperative period | 
| assessment in perioperation-Rate of Operative Complication | Complication rate after operation before discharge | perioperative period | 
| assessment in perioperation-Mortality of perioperation | Mortality of perioperation 20 days before operation and 30 days after operation | perioperative period | 
| assessment in perioperation-Days of Hospitalization | Days of Hospitalization after operation | perioperative period | 
| assessment in perioperation-Thoracic Drainage | Thoracic Drainage days | perioperative period | 
| assessment in perioperation-Quantity of bleeding | blood lose during operation | perioperative period | 
| assessment in perioperation-Time of operation | the time from open thoracic cavity to the closure of the thoracic cavity | perioperative period | 
| Quality of life | ECOG, KPS, NRS-2002, EORTC QLQ-ST018, EORTC QLQ-C30 | 1 years | 
| efficacy of neo-adjuvant chemotherapy--response rate | Criteria:Response Evaluation Criteria in Solid Tumors，RECIST. Pathologic Complete Response Rate. Pathologic Response Rate. | 1-4 days before operation | 
| toxicities of neo-adjuvant chemotherapy | According to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0(CTC AE3.0). The complete rate of protocol | from chemotherapy to perioperative period | 
| prognostic factors | prognostic factors for overall survival of both groups | 5 years | 
| predictive factors | predictive factors for the efficiency of neo-adjuvant chemotherapy | 2 years |