Definitive Concurrent Chemoradiotherapy With Docetaxel Plus Cisplatin Versus 5-fluorouracil Plus Cisplatin in Patients With Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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In this phase II study, the investigators aim to evaluated the efficacy and toxicity of definitive concurrent chemoradiotherapy (CCRT) with docetaxel plus cisplatin (DP regimen) versus 5-fluorouracil plus cisplatin (PF regimen) in patients with esophageal squamous cell carcinoma (ESCC).

Detailed Description
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Esophageal cancer is one of the most fatal malignancies worldwide. Radical surgery has been the primary treatment for patients with resectable esophageal cancer. For medically unfit patients or medically fit patients who decline surgery, definitive radiotherapy plus concurrent chemotherapy has been established as a standard treatment. Since the 1980' s, the most widely used chemotherapeutic regimen in combination with radiotherapy for esophageal cancer was cisplatin (CDDP) plus 5-fluorouracil (5-FU) (the PF regimen). However, locoregionally persistent or recurrent diseases were still quite common and survival remained poor. Several previous studies conducted by the radiation therapy oncology group (RTOG) explored the efficacy of radiation dose escalation, but all results turned out disappointing. And studies incorporating intensified PF regimen or new-generation cytotoxic agents such as paclitaxel and oxaliplatin did not show any advantage over the standard-dosage PF regimen either. In this phase II study, the investigators aim to evaluated the efficacy and toxicity of definitive concurrent chemoradiotherapy (CCRT) with docetaxel plus cisplatin (DP regimen) versus 5-fluorouracil plus cisplatin (PF regimen) in patients with esophageal squamous cell carcinoma (ESCC).

Official Title
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Definitive Concurrent Chemoradiotherapy With Docetaxel Plus Cisplatin Versus 5-fluorouracil Plus Cisplatin in Patients With Esophageal Squamous Cell Carcinoma: a Phase II Randomized Controlled Trial

Conditions
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Esophageal Neoplasm, Chemoradiation

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with histologically proven squamous cell carcinoma of the esophagus stage II-IVA disease, including metastatic celiac or cervical nodes, according to the sixth edition of American Joint Committee on Cancer (AJCC) staging system for esophageal cancer aged between 18 and 70 years Karnofsky Performance Status (KPS) score ≥ 70 adequate bone marrow function (leukocyte count ≥ 4000/uL, platelet count ≥ 100,000/uL), adequate liver function (serum alanine aminotransferase (ALT) level and serum aspartate aminotransferase (AST) level < twice the upper limit of normal, and serum bilirubin level of <1.5 mg/dL), and adequate renal function (creatinine clearance ≥ 50 mL/min) no other serious medical conditions life expectancy ≥ 3 months written informed consent Exclusion Criteria: detection of distant metastasis (excluding metastatic celiac or cervical nodes) before treatment before treatment known allergy to CDDP, 5-FU, or docetaxel pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: PF group<br>This is the active comparator group. All patients in this group will receive concurrent chemoradiotherapy with PF regimen (5-fluorouracil plus cisplatin). | Drug: Fluorouracil<br>* Radiotherapy: All patients underwent conventional radiotherapy, 1.8-2.0 Gy per fraction and 5 fractions per week. The prescribed dose was 60-64 Gy to PTV1 and 50 Gy to PTV2. Patients received either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT). 3D-CRT treatment plans were calculated by Pinnacle planning system and IMRT treatment plans were calculated by Monacle planning system. All patients were treated with a 6-MV or 8-MV linear accelerator. Chemotherapy: All patients received two cycles of chemotherapy concurrently with radiotherapy. Patients assigned to the PF group received two cycles of PF regimen (cisplatin 80 mg/m2 delivered on day 1 and 5-FU 1000 mg/m2 continuous infusion over 24 hours daily on days 1-4) at a 3-week interval. In cases of grade 4 hematologic toxicity or severe non-hematologic toxicities, dose adjustment was performed in the subsequent chemotherapy cycle.<br>* Other names: cisplatin;|
| Experimental: DP group<br>This is the experimental group. All patients in this group will receive concurrent chemoradiotherapy with DP regimen (docetaxel plus cisplatin). | Drug: Docetaxel<br>* Radiotherapy: All patients underwent conventional radiotherapy, 1.8-2.0 Gy per fraction and 5 fractions per week. The prescribed dose was 60-64 Gy to PTV1 and 50 Gy to PTV2. Patients received either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT). 3D-CRT treatment plans were calculated by Pinnacle planning system and IMRT treatment plans were calculated by Monacle planning system. All patients were treated with a 6-MV or 8-MV linear accelerator. Chemotherapy: All patients received two cycles of chemotherapy concurrently with radiotherapy. Patients assigned to the DP group received two cycles of DP regimen (docetaxel 60 mg/m2 delivered on day 1 and cisplatin 80 mg/m2 delivered on day 1) at a 3-week interval. In cases of grade 4 hematologic toxicity or severe non-hematologic toxicities, dose adjustment was performed in the subsequent chemotherapy cycle.<br>* Other names: cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | From the date of randomization until the date of death, up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response rate |  | From the date of randomization until six weeks after treatment completion. | 
| Progress Free Survival (PFS) |  | From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years. | 
| Acute treatment-related toxicities |  | From the date of randomization until six months after treatment completion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal squamous cell carcinoma, concurrent chemoradiotherapy, docetaxel, cisplatin, 5-fluorouracil