Combination Chemotherapy and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Esophageal Cancer

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of docetaxel when administered with carboplatin and capecitabine as neoadjuvant induction therapy in patients with locally advanced esophageal cancer.

Secondary

• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Determine the clinical and pathological response in these patients treated with neoadjuvant induction therapy comprising docetaxel, carboplatin, and capecitabine followed by chemoradiotherapy with capecitabine.

OUTLINE: This is an open-label, dose-escalation study of docetaxel.

• Induction therapy: Patients receive docetaxel IV and carboplatin IV over 30-60 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 2 courses.

Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Approximately 7 days after completion of induction therapy, patients proceed to chemoradiotherapy.

• Chemoradiotherapy: Patients receive oral capecitabine twice daily on days 1-42 and undergo radiotherapy once daily, 5 days a week, on days 1-40.
• Surgery: Approximately 4-8 weeks after completion of chemoradiotherapy, patients undergo surgery.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed esophageal or gastroesophageal junction cancer

• Locally advanced disease, meeting 1 of the following staging criteria:

• T3, N0, M0 disease
• Any T, N1, M0 disease
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL

Hepatic

• Bilirubin normal
• Meets 1 of the following criteria:

• Alkaline phosphatase (AP) normal AND AST/ALT ≤ 5 times upper limit of normal (ULN)
• AP ≤ 2.5 times ULN AND AST/ALT ≤ 1.5 times ULN
• AP ≤ 5 times ULN AND AST/ALT normal

Renal

• Creatinine ≤ 2.0 mg/dL
• Creatinine clearance ≥ 80 mL/min

Cardiovascular

• No uncontrolled congestive heart failure
• No symptomatic coronary artery disease
• No uncontrolled arrhythmias
• No myocardial infarction within the past 12 months
• No other uncontrolled clinically significant cardiac disease

Gastrointestinal

• Able to swallow tablets
• Intact upper gastrointestinal tract
• No malabsorption syndrome

Immunologic

• No history of unanticipated severe reaction to fluoropyrimidine
• No known hypersensitivity to fluorouracil
• No severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No serious infection that requires continuous antibiotic therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• No other prior or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of seizures
• No history of serious psychiatric illness that would preclude study compliance or giving informed consent
• No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy

Radiotherapy

• No prior radiotherapy

Other

• More than 28 days since prior investigational drugs
• No concurrent warfarin for active anticoagulation