OBJECTIVES:

Primary

• Determine the efficacy and toxicity of neoadjuvant and adjuvant capecitabine and oxaliplatin in patients with resectable liver metastases secondary to colorectal cancer who are undergoing surgery.
• Determine the rates of R0 resection in patients treated with this regimen before surgery.

Secondary

• Determine the response rate in patients treated with this regimen.
• Determine the resectability in the subsets of patients defined as resectable preoperatively and treated with this regimen.
• Determine improvement in survival associated with downstaging based on metastatic colorectal prognostic score in patients treated with this regimen.
• Determine the disease-free and overall survival of patients treated with this regimen.
• Correlate drug-specific biomarkers with clinical response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Surgery: Four to six weeks after the completion of chemotherapy, patients undergo surgical resection of the tumor.
• Adjuvant chemotherapy: Patients with satisfactory response to therapy receive 4 additional courses of oxaliplatin and capecitabine after surgery.

Patients are followed at 4-6 weeks after surgery, every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatic colorectal metastasis by percutaneous hepatic biopsy

  • Imaging evidence of liver metastasis by CT helical scan

• Resectable disease, as determined by a surgeon with hepatic surgery expertise (at least 10 resections performed per year)

  • Resectable, defined as a sparing of 2 adjacent liver segments with adequate vascular inflow and outflow and hepatic remnant volume
  • Minor resections (less than a hemihepatectomy) or major resections (hemihepatectomy or extended hepatectomy) allowed
  • Bilobar resection allowed, including atypical resections
• No evidence of extrahepatic disease by chest x-ray or CT scan of the chest, abdomen, and pelvis

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than 2 mg/dL
• AST and ALT no greater than 300 IU/L
• No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis) that would preclude surgical resection of metastases

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except completely resected nonmelanoma skin cancer or carcinoma in situ of the cervix
• No preexisting grade 2 or greater peripheral neuropathy
• No concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic therapy
• No concurrent sargramostim (GM-CSF)

Chemotherapy

• More than 6 months since prior adjuvant fluorouracil-based chemotherapy
• No prior chemotherapy for liver metastasis
• No prior oxaliplatin for colorectal cancer
• No prior or concurrent hepatic artery infusion chemotherapy for metastatic disease

Endocrine therapy

• Not specified

Radiotherapy

• No prior or concurrent radiotherapy for metastatic disease

Surgery

• No prior or concurrent radiofrequency ablation for metastatic disease
• No prior or concurrent cryotherapy/other ablative techniques for metastatic disease

Other

• No other concurrent investigational therapy
• No concurrent oral anticoagulation