RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus

Study Overview
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Brief Summary
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The purpose of the study was to test a null hypothesis that a combined modality treatment of esophageal cancer with neoadjuvant chemotherapy or chemoradiotherapy is equivalent to surgery alone and what are the benefits from adding irradiation to chemotherapy in neoadjuvant treatment of esophageal cancer.

Detailed Description
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The choice of the most beneficial method of treatment in esophageal cancer remains controversial and is the subject of vigorous debate. Surgery is still regarded as the principle modality among treatment strategies, with longterm survival achieved mainly in less advanced cases. More advanced cases, diagnosed more frequently, are more problematic in selection of the optimal therapeutic method. One of the options for improving treatment outcome in patients with advanced esophageal cancer is combined modality treatment with chemo- and chemoradiotherapy. Currently available RCTs have tested preoperative chemotherapy or chemoradiotherapy separately in comparison to surgery alone. Moreover, we do not know from these trials what is the added value of irradiation in a combined modality therapy over a preoperative chemotherapy. Another drawback of available RCTs is combining 2 different biological cancer entities: adenocarcinoma and squamous cell carcinoma of the esophagus as well as carcinoma of the esophagus and gastro-esophageal junction. That were the reasons for designing our trial testing 3 principal modes of esophageal cancer therapy: surgery vs. chemotherapy + surgery vs. chemoradiotherapy + surgery on homogenous population of esophageal cancer patients with single pathological type - squamous cell carcinoma affecting thoracic esophagus.

Official Title
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Possibilities for Improvement of an Outcome of the Treatment in Squamous Cell Carcinoma of the Thoracic Esophagus - a Multicenter Randomized Clinical Phase III Trial.

Conditions
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Esophageal Neoplasms, Squamous Cell Cancer

Intervention / Treatment
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* Procedure: transthoracic esophagectomy 2-field extended lymphadenectomy
* Drug: neoadjuvant chemotherapy (cisplatin, 5-fluorouracil)
* Radiation: neoadjuvant chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Histopathologically proven, clinically stage II-III (cTNM according to AJCC/UICC classification), primary squamous cell carcinoma of the thoracic esophagus Patients' age above 18 years General condition with Karnofsky performance status of >70 Circulatory and pulmonary capacity at normal range (FEV1 >60%; FVC >60%, NYHA I-II, cardiac output >40%) Normal function of the bone marrow (RBC >3,5 T/l; PLT >100 G/l) Normal renal (creatinine <1.5 of the upper limit) and liver (AST or ALT <2,5 of the upper limit or bilirubin <1,5 of the upper limit) function Exclusion Criteria: Metastatic disease Synchronous malignancy History of other cancer within 5 years prior to esophageal cancer treatment History of allergic reaction to cisplatin of 5-fluorouracil Systemic infection Pregnancy or female patients in childbearing age without proper contraceptives.

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 |
| --- | --- |
| Active Comparator: S<br>esophagectomy | Procedure: transthoracic esophagectomy 2-field extended lymphadenectomy<br>* right thoracotomy, mobilization of the esophagus, mediastinal lymph node dissection, laparotomy, gastric tube formation, abdominal lymph node dissection, anastomosis in the neck<br>|
| Experimental: CHTS<br>neoadjuvant chemotherapy followed by esophagectomy | Drug: neoadjuvant chemotherapy (cisplatin, 5-fluorouracil)<br>* 21-day combination systemic chemotherapy regimen consisted of a continuous infusion of cisplatin (20mg/m2/day) on days 1-5, 17-21 and 5-fluorouracil at 300mg/m2/day on days 1-21 followed by 3-phase transthoracic esophagectomy with 2-field extended lymphadenectomy after 3 week interval<br>|
| Experimental: CHRTS<br>neoadjuvant chemoradiotherapy followed by esophagectomy | Radiation: neoadjuvant chemoradiotherapy<br>* 21-day combination systemic chemotherapy regimen consisted of a continuous infusion of cisplatin (20mg/m2/day) on days 1-5, 17-21 and 5-fluorouracil at 300mg/m2/day on days 1-21 with concurrent external beam fractionated irradiation to a total dose of 30Gy (2Gy fractions on days 1-5, 8-12, 15-19) followed by 3-phase transthoracic esophagectomy with 2-field extended lymphadenectomy after 3 week interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean, median, 1-year, 3-year, 5-year overall survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicity-related morbidity and mortality |  | 30-day | 
| postoperative morbidity and mortality |  | 30-day | 
| clinical and pathological response rates |  | 60-day | 
| curative resection rate |  | 30-day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophagectomy, chemotherapy, chemoradiotherapy, combined modality therapy