Celecoxib, Paclitaxel, and Carboplatin in Treating Patients With Cancer of the Esophagus

• Pathological response rate at time of surgical resection [ Time Frame: At completion of pathology report. ] [ Designated as safety issue: No ]
  

• Clinical response rate [ Time Frame: At the time of tumor assessment obtained prior to definitive surgery approximately 1-2 weeks prior to surgical resection. ] [ Designated as safety issue: No ]
  
• Disease-free survival [ Time Frame: From start of treatment to time of recurrent disease measured postoperatively every 6 months for 18 months. ] [ Designated as safety issue: No ]
  
• Overall survival [ Time Frame: 18 months after surgery ] [ Designated as safety issue: No ]
  
• Toxicities and safety [ Time Frame: 30 days after completion of study treatment. ] [ Designated as safety issue: Yes ]
  

Drug: carboplatin
Dosed to an AUC of 6 by the Calvert formula, intravenously over 1 hour after paclitaxel on days 1, 22, and 43.
Drug: celecoxib
400 mg orally BID begins 3-7 days before the first dose of chemotherapy to the morning of surgery. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year total, that is, 1 year from the date of surgery + 2 weeks unless tumor recurrence is documented.
Other Name: Celebrex
Drug: paclitaxel
200 mg/m2 as a 3-hour intravenous infusion on days 1, 22, and 43.
Other Name: Taxol
Procedure: adjuvant therapy
1. Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.
2. Operation will be performed within 6-12 hours from the last dose of celecoxib.
3. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.
4. Celecoxib 400 mg orally BID will resume post-operatively 4-8 weeks if there is adequate wound healing and will be continued for 1 year.
Procedure: conventional surgery
1. Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.
2. Operation will be performed within 6-12 hours from the last dose of celecoxib.
3. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.
Procedure: neoadjuvant therapy
1. Surgery will be performed 3-4 weeks after the third dose of paclitaxel and carboplatin.
2. Operation will be performed within 6-12 hours from the last dose of celecoxib.
3. Surgery will include an esophagectomy as well as a complete mediastinal and abdominal lymph node dissection.

OBJECTIVES:

Primary

• Determine the rate of complete pathological response and/or minimal residual microscopic disease in patients with squamous cell or adenocarcinoma of the esophagus treated with preoperative celecoxib, paclitaxel, and carboplatin.

Secondary

• Determine the clinical response rate of patients treated with this regimen.
• Determine the chemotherapy-related toxicity of this regimen in these patients.
• Determine the time to progression, disease-free survival, and overall survival of patients treated with this regimen.

OUTLINE: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning 3-7 days before the first dose of chemotherapy and continuing until the morning of planned surgical resection (between days 64 and 71). Approximately 28-56 days after resection, patients may resume oral celecoxib twice daily and continue for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed periodically for 18 months after surgery.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 18 months.