Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so it can be removed during surgery. It is not yet known if surgery is more effective with or without radiation therapy and chemotherapy in treating esophageal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without radiation therapy and chemotherapy in treating patients who have esophageal cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with resectable thoracic esophageal cancer treated with neoadjuvant radio-chemotherapy and surgery versus surgery alone. Compare the disease-free survival of patients treated with these regimens. Compare the surgical mortality and morbidity of patients treated with these regimens. Compare the resectability of patients treated with these regimens. Determine the validation of new prognostic factors for survival of these patients and/or the efficacy of this neoadjuvant treatment. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to histology (epidermoid carcinoma vs adenocarcinoma vs undifferentiated carcinoma), stage (I vs IIA vs IIB), tumor location (above the carina vs below the carina), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy daily 5 days a week for 5 weeks. Patients receive fluorouracil IV continuously on days 1-4 and 29-32 and cisplatin IV on days 1 or 2 and 29 or 30 (or a lower dose on days 1-5 and 29-33). Within 4-8 weeks after completion of radio-chemotherapy, patients undergo surgical resection. Arm II: Patients undergo surgical resection. Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 380 patients (190 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Randomized Study of Pre-Operative Radio-Chemotherapy Versus Surgery Alone in Thoracic Esophageal Cancer Deemed to be Resectable

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage I or II thoracic esophageal cancer Tumor no greater than 3 cm with no invasion of mediastinal structures with or without extension to the lymph nodes (T1-2, N0-1, M0) OR Tumor greater than 3 cm with no invasion of mediastinal structures and no adenopathy greater than 1 cm (T3, N0, M0) Epidermoid carcinoma or adenocarcinoma Previously untreated Deemed resectable with curative intent No carcinoma in situ No small cell anaplastic carcinoma (i.e., chromogranin negative) No small cell neuroendocrine carcinoma (i.e., chromogranin positive) No multifocal esophageal carcinoma (i.e., 2 or more distinct lesions 5 or more cm apart) No involvement of the pharyngoesophageal junction and the first 4 cm of the esophagus (i.e., where the proximal edge of the tumor is less than 19 cm from the dental arch) No evidence of extension to the tracheobronchial tree at endoscopy, ultrasound, or CT scan (simple compression allowed) No signs of mediastinal involvement on CT scan No palpable subclavicular lymph nodes or involvement after cytology needle aspiration No lymph nodes from the origin of the celiac greater than 1 cm on CT scan Perigastric lymph nodes far from the celiac trunk and deemed resectable allowed unless tumor is more than 30 mm on CT scan PATIENT CHARACTERISTICS: Age Under 75 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic SGOT/SGPT ratio no greater than 1 Albumin at least 35 g/L Total protein greater than 80% No liver cirrhosis with previous failure No ascites No jaundice No rupture of varicose esophageal veins No presence of varicose esophageal veins Renal Creatinine no greater than 1.25 times normal Cardiovascular Arterial O_2 greater than 60 mm Hg Arterial CO_2 no greater than 45 mm Hg No myocardial infarction within the past 6 months No progressive coronary artery disease grade 2 or greater No recent left ventricular failure No arterial disease stage II-IV Pulmonary FEV_1 greater than 1 L/sec Other Able to receive either study treatment No recurrent paralysis No weight loss greater than 10% from baseline No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix Not pregnant Fertile patients must use effective contraception during and for 3 months after completion of chemotherapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Maximum Age: 74 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: CHIMIORADIOTHERAPIE SUIVIE DE CHIRURGIE<br>CHIMIORADIOTHERAPIE SUIVIE DE CHIRURGIE | Drug: cisplatin<br> <br> Drug: fluorouracil<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: CHIRURGIE SEULE<br>CHIRURGIE SEULE | Procedure: conventional surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overal survival |  | 2010 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence free survival |  | 2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage I esophageal cancer, stage II esophageal cancer