Oxaliplatin, Capecitabine, and Radiation Therapy in Patients Undergoing Surgery for Stage II, III, IV Esophageal Cancer

OBJECTIVES:

Primary

• Determine the complete pathologic response (complete response [CR]) rate in patients with stage II-IVA esophageal cancer treated with neoadjuvant oxaliplatin, capecitabine, and radiotherapy.

Secondary

• Determine the clinical efficacy and toxicity of this regimen in these patients.
• Determine the quality of life of patients treated with this regimen.
• Identify basal expression and changes in gene expression that relate to CR, relapse, and survival of patients treated with this regimen.

OUTLINE:

• Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 (weeks 1, 3, and 5). Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38 and receive oral or enteral capecitabine twice daily on the same days they undergo radiotherapy.
• Surgery: At 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients who are eligible undergo esophagectomy.
• Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and oral or enteral capecitabine twice daily on days 1-5, 8-12, 15-19, 22-26, and 29. Treatment repeats approximately every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor biopsies periodically. Collected samples are analyzed by gene expression studies, microarray analysis, and real-time quantitative reverse transcriptase-PCR to identify basal expression and changes in gene expression.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of squamous cell carcinoma of the esophagus or adenocarcinoma of the esophagus

• Stage II-IVA disease as determined by clinical staging, including endoscopy and CT scan with or without endoscopic ultrasound
• Bulk of gastroesophageal junction tumor should be in the esophagus
• Bronchoscopy with biopsy and cytology required if primary esophageal cancer is < 26 cm from incisors
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy > 4 months
• WBC > 4,000/mm³
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 9 g/dL
• Bilirubin normal
• Creatinine normal
• AST < 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• Able to take oral medication or undergo enteral administration of medication
• No peripheral neuropathy ≥ grade 2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 90 days after completion of study treatment
• No hypersensitivity to platinum compounds, fluoropyrimidines, or antiemetics administered in combination with protocol-directed chemotherapy
• No concurrent uncontrolled illness, including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would preclude study compliance
• No history of second malignancy except for curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

• Other cured tumors allowed at discretion of the principal investigator
• No known HIV or hepatitis B or C (active and/or previously treated)

PRIOR CONCURRENT THERAPY:

• No prior therapy for esophageal cancer
• No other concurrent investigational agents