Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients With Esophageal or Gastroesophageal Junction Cancer

OBJECTIVES:

Primary

• Determine the pathologic complete response in patients with adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant therapy comprising capecitabine, oxaliplatin, and radiotherapy.

Secondary

• Determine the clinical response rate in patients treated with this regimen.
• Determine the recurrence rate, time to progression, and patterns of failure in patients treated with this regimen.
• Characterize the toxicity profile of this regimen in these patients.

OUTLINE:

• Induction therapy: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
• Combination chemoradiotherapy: Patients then receive oxaliplatin IV over 2 hours once weekly for 6 weeks. Patients also receive concurrent oral capecitabine twice daily and undergo radiotherapy once daily 5 days a week for 5½ weeks in the absence of disease progression or unacceptable toxicity.
• Surgery: Patients undergo surgical resection at 4-8 weeks after completion of chemoradiotherapy.

After completion of study treatment, patients are followed every 3 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction

• Stage I-IVA disease
• No distant metastatic disease (other than regional lymph nodes)
• No evidence of CNS metastases

• CNS metastases stable for > 3 months allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Consuming ≥ 1,500 calories daily
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No pre-existing neuropathy
• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No known hypersensitivity to fluorouracil
• No known DPD deficiency
• No known hypersensitivity to any of the components of oxaliplatin
• No significant active infection or other severe complicated medical illness
• No clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias not well controlled with medication)
• No myocardial infarction within the past 12 months
• No history of uncontrolled seizures, CNS disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake
• No malabsorption syndrome
• No other active malignancy within the past 3 years except cervical carcinoma in situ or nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior participation in any investigational drug study
• No prior pelvic or thoracic radiotherapy