Radiation Therapy and Paclitaxel, Carboplatin, and Fluorouracil Followed by Esophagectomy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy and giving them before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: This phase II trial is studying how well giving radiation therapy together with combination chemotherapy followed by esophagectomy works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction.

Detailed Description
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OBJECTIVES: Determine the pathologic complete response rate in patients with locally advanced cancer of the esophagus or gastroesophageal junction treated with radiotherapy administered concurrently with paclitaxel, carboplatin, and fluorouracil before esophagectomy. Determine the tolerability of this regimen in these patients. Determine the tumor response rate in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. Assess the relationship between the presence of genetic polymorphisms in these patients and the toxicity of this regimen. OUTLINE: This is a multicenter study. Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery. Patients are followed every 3 months for 4 years.

Official Title
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A Phase II Trial of Preoperative Radiation and Chemotherapy (Paclitaxel, Carboplatin, and Continuous Infusion 5-FU) for Locally Advanced Esophageal Cancer

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: carboplatin
* 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 or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastroesophageal junction Surgically resectable disease (T1-3; NX, N0, or N1; M1a) T4 tumors that are not unequivocally unresectable allowed Celiac lymph node (stations 15-20) involvement allowed Must be considered a potential surgical candidate by a thoracic or general surgeon No supraclavicular lymph node involvement by palpation, biopsy, or radiograph (greater than 1.5 cm) No distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Patients with ECOG 2 must be considered good candidates for study by treating oncologists Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 3 times ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular No New York Heart Association class III or IV heart disease Other No uncontrolled infection No other severe underlying disease that would preclude study participation No grade 2 or greater peripheral neuropathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for esophageal cancer Endocrine therapy Not specified Radiotherapy No prior radiotherapy to anticipated fields of study radiotherapy Surgery Not specified Other No concurrent diuretics No concurrent amifostine

Ages Eligible for Study
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Minimum Age: 18 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: carboplatin + paclitaxel + fluorouracil + radiation + surgery<br>Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery. Patients are followed every 3 months for 4 years. | Drug: carboplatin<br> <br> Drug: fluorouracil<br> <br> Drug: paclitaxel<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of successes |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity-free rate |  | Up to 4 years | 
| Clinical tumor response |  | Up to 4 years | 
| Pathologic tumor response |  | Up to 4 years | 
| Time to disease progression |  | Up to 4 years | 
| Surgical outcome |  | Up to 4 years | 
| Survival |  | Up to 4 years | 
| Time to treatment failure |  | Up to 4 years | 
| Quality of life |  | Up to 4 years | 

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