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

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed esophageal cancer of 1 of the following cellular types:

• Squamous cell
• Adenocarcinoma
• Potentially resectable disease
• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• No bleeding disorder

Hepatic

• Bilirubin normal
• AST and ALT less than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No significant history of unstable cardiovascular disease
• No inadequately controlled hypertension
• No angina
• No myocardial infarction within the past 6 months
• No ventricular cardiac arrhythmias requiring medication
• No congestive heart failure that would preclude study therapy

Pulmonary

• Pulmonary function acceptable for surgery
• No interstitial pneumonia
• No interstitial fibrosis

Gastrointestinal

• No history of peptic ulcer disease
• No irritable bowel syndrome
• No inflammatory bowel disease
• No chronic diarrhea
• No bowel obstruction within the past 5 years

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
• No hypersensitivity to paclitaxel or carboplatin
• No other serious underlying medical condition that would preclude study therapy
• No significant psychiatric illness that would preclude study compliance
• No uncontrolled diabetes mellitus
• No uncontrolled infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent chronic steroid use except inhaled mometasone or fluticasone

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 3 weeks since other prior clinical trial therapy
• At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs)
• No concurrent chronic NSAID use (7 or more days of continuous therapy per month OR 3 or more days of therapy per week)
• No other concurrent investigational agents
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital)
• No other concurrent cyclo-oxygenase (COX)-2 inhibitors
• No concurrent lithium or fluconazole
• Concurrent low-dose aspirin (325 mg/day or less) allowed for cardiovascular prophylaxis