Drugs used in chemotherapy, such as capecitabine and oxaliplatin, use different ways to stop
tumor cells from dividing so they stop growing or die. Giving capecitabine and oxaliplatin
before surgery may shrink the tumor so that it can be removed. Giving capecitabine and
oxaliplatin after surgery may kill any remaining tumor cells. This phase II trial is
studying how well capecitabine and oxaliplatin work when given before and after surgery in
treating patients with resectable liver metastases that is secondary to colorectal cancer
I. 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.
II. Determine the rates of R0 resection in patients treated with this regimen before
I. Determine the response rate in patients treated with this regimen. II. Determine the
resectability in the subsets of patients defined as resectable preoperatively and treated
with this regimen.
III. Determine improvement in survival associated with downstaging based on metastatic
colorectal prognostic score in patients treated with this regimen.
IV. Determine the disease-free and overall survival of patients treated with this regimen.
V. Correlate drug-specific biomarkers with clinical response in patients treated with this
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.
- 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,
- Performance status - Zubrod 0-1
- 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
- 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
- Creatinine no greater than 1.5 mg/dL
- Creatinine clearance 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- 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
- No concurrent biologic therapy
- No concurrent sargramostim (GM-CSF)
- 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
- No prior or concurrent radiotherapy for metastatic disease
- No prior or concurrent radiofrequency ablation for metastatic disease
- No prior or concurrent cryotherapy/other ablative techniques for metastatic disease
- No other concurrent investigational therapy
- No concurrent oral anticoagulation