Combination Chemotherapy Followed By Chemoradiotherapy, With or Without Surgery, in Treating Patients With Resectable Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as paclitaxel, fluorouracil, and cisplatin use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells PURPOSE: This phase II trial is studying how well combination chemotherapy followed by chemoradiotherapy, with or without surgery, works in treating patients with resectable locally advanced cancer of the esophagus or gastroesophageal junction.

Detailed Description
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OBJECTIVES: Determine the feasibility of treatment with paclitaxel, cisplatin, and fluorouracil followed by chemoradiotherapy and possible surgical salvage in patients with resectable locally advanced carcinoma of the esophagus or gastroesophageal junction. Determine the overall and disease-free survival of patients treated with this regimen. Determine the treatment-related toxicity of this regimen in these patients. Determine the tolerance to surgical salvage in patients treated with this regimen. Determine the morbidity and mortality of surgical salvage in patients treated with this regimen. OUTLINE: This is a multicenter study. Induction therapy: Patients receive fluorouracil (5-FU) IV continuously over 96 hours beginning on days 1 and 29; cisplatin IV over 1 hour on days 1-5 and 29-33; paclitaxel IV over 2 hours on days 1 and 29; and pegfilgrastim subcutaneously (SC) on days 6 and 34 OR filgrastim (G-CSF) SC on days 6-15 and 34-42. Treatment continues in the absence of unacceptable toxicity. Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on days 57-61 and 5-FU IV continuously on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96. Patients concurrently undergo external beam radiotherapy on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96. Patients with residual or recurrent esophageal disease 4-6 weeks after completion of chemoradiotherapy may undergo salvage esophagectomy. Patients are followed periodically. PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study within 18 months.

Official Title
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A Phase II Study Of Paclitaxel-Based Chemoradiotherapy Regimen With Selective Surgical Salvage For Resectable Locoregionally Advanced Carcinoma Of The Esophagus

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Biological: filgrastim
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: fluorouracil
* Drug: paclitaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction Primary (non-recurrent) disease Amenable to resection Stage greater than T1, N0 by endoscopic ultrasound Must be entirely confined to the esophagus or gastroesophageal junction and periesophageal soft tissue Tumor may not extend more than 2 cm into the stomach No multiple primary carcinomas of the esophagus No cervical esophageal carcinoma or tumors less than 5 cm from cricopharyngeus No evidence of disseminated cancer Suggestion of liver metastases by positron emission tomography must be proven negative by biopsy or other imaging studies Palpable supraclavicular nodes must be negative for cancer by biopsy Bronchoscopy required for lesions less than 26 cm from the incisors to exclude tracheoesophageal fistula or invasion No celiac adenopathy greater than 2 cm PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Not specified Renal Creatinine no greater than 1.5 mg/dL AND/OR Creatinine clearance at least 65 mL/min Calcium no greater than 11 mg/dL Cardiovascular No uncontrolled heart disease No uncontrolled hypertension Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to comprehend study requirements and considered likely to comply with study parameters No other malignancy within the past 5 years except curable nonmelanoma skin cancer or carcinoma in situ of the cervix No uncontrolled diabetes No hypersensitivity to E. coli-derived products PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 5 years since prior systemic chemotherapy Endocrine therapy Not specified Radiotherapy No prior chest or upper abdomen radiotherapy Surgery No prior esophageal or gastric surgery Other No concurrent photodynamic therapy No other concurrent investigational agents for esophageal carcinoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ChemoRT and selective surgery<br>Induction therapy of fluorouracil, cisplatin, paclitaxel, and pegfilgrastim OR filgrastim, then chemoradiotherapy of concurrent cisplatin and fluorouracil with external beam radiotherapy (RT), followed by selective salvage therapy. | Biological: filgrastim<br>* During induction therapy, patients ≤ 70 kg will receive 300 μg OR patients >70 kg will receive 480 μg subcutaneously on days 6-15 and 34-42.<br>* Other names: G-CSF;Biological: pegfilgrastim<br>* During induction therapy, patients receive 6 mg subcutaneously on days 6 and 34.<br>* Other names: PEG-G-CSF;Drug: cisplatin<br>* During induction therapy, patients receive 15 mg/m^2/day by IV over 1 hour on days 1-5 and 29-33. During radiotherapy, patients receive 15 mg/m^2/day by IV over 1 hour beginning on days 57-61.<br>Drug: fluorouracil<br>* During induction therapy, patients receive 650 mg/m^2/day by IV continuously over 96 hours beginning on days 1 and 29. During radiotherapy, patients receive 300 mg/m^2/day by IV continuously over 96 hours beginning on day 57 for 5 cycles.<br>* Other names: 5-FU;Drug: paclitaxel<br>* During induction therapy, patients receive 200 mg/m^2/day by IV over 2 hours on days 1 and 29.<br>Procedure: conventional surgery<br>* Patients with residual or recurrent esophageal disease 4-6 weeks after completion of chemoradiotherapy may undergo salvage esophagectomy.<br>Radiation: radiation therapy<br>* External beam radiotherapy with megavoltage linear accelerators (> 6 MV) will be used to deliver multiple (> 2) field techniques. Patients will be treated 5 days/week at 1.8 Gy/day for 28 days for a total dose of 50.4 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (1-year Rate Reported) | One-year survival estimate is reported. Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 1 year. On the basis of a 1-year survival rate of 60% from the Radiation Therapy Oncology Group (RTOG) esophageal database, 38 analyzable patients with a 1-year survival rate of 77.5% or better was needed for this trial to be deemed promising enough for development of a Phase III protocol (type I error of 0.05 and type II error of 0.20). | From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Major (Grade 4) Acute Treatment-related Toxicities |  | From start of chemotherapy to surgery or 2 months after chemoradiation (for patients not undergoing surgery). | 
| Frequency of Patients With Persistent or Recurrent Disease Eligible for Surgical Salvage Resection |  | Analysis occurs with the primary outcome measure. | 

 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 II esophageal cancer, stage III esophageal cancer