Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer

OBJECTIVES:

- Determine the surgical resectability rate of patients with unresectable hepatic
metastases secondary to metastatic colorectal adenocarcinoma treated with oxaliplatin,
fluorouracil, leucovorin calcium, and cetuximab.

- Determine the response rate and overall survival of patients treated with this regimen.

- Determine the quality of life of patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1
and 8. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2
hours on day 1 and fluorouracil IV continuously on days 1-2. Treatment repeats every 2 weeks
in the absence of disease progression or unacceptable toxicity, for a minimum of 12 courses
or until deemed to have resectable disease.

Quality of life is assessed at baseline and prior to each treatment course.

Patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 67-73 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

- History of completely resected primary adenocarcinoma of the colon or rectum

- No gross or microscopic evidence of residual disease

- Liver metastases, meeting 1 of the following criteria:

- Not optimally resectable

- Requires resection of all 3 major hepatic veins, the portal vein bifurcation, or
the retrohepatic vena cava

- Includes the main right or main left portal vein and the main hepatic vein of
the opposite lobe

- Requires more than a right or left trisegmentectomy

- At least 6 metastatic lesions distributed diffusely in both lobes of the liver

- Measurable disease

- At least 1 measurable lesion ≥ 20 mm

- No evidence of extrahepatic metastases by physical examination or x-ray

- No previously resected extrahepatic metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- AST ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ ULN

- No preexisting chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis)
that would preclude surgical resection of metastases

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No myocardial infarction within the past 6 months

- No clinical evidence of congestive heart failure

- No New York Heart Association class III-IV heart disease

- No significant cardiac disease

- No uncontrolled hypertension

- No unstable angina

- No congestive heart failure

- No uncontrolled arrhythmias

Gastrointestinal

- Adequate oral nutrition with estimated caloric intake of ≥ 1,500 calories/day

- No severe anorexia or frequent nausea and/or vomiting

- No history of gastrointestinal bleeding that has not been appropriately addressed

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to tolerate major surgery

- No prior allergic reaction or known sensitivity to chimerized or murine monoclonal
antibody therapy

- No documented presence of human anti-mouse antibodies

- No known allergy to other platinum compounds

- No other malignancy within the past 5 years except basal cell or squamous cell skin
cancer, carcinoma in situ, or tumors associated with less than 10% probability of
death within 5 years of diagnosis

- No preexisting neuropathy ≥ grade 2

- No symptomatic pulmonary fibrosis or interstitial pneumonitis

- No uncontrolled bacterial or viral infection

- HIV negative

- No fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No colony-stimulating factors within 24 hours of day 1 of each course

- No concurrent immunotherapy

Chemotherapy

- At least 1 year since prior adjuvant systemic fluorouracil with or without levamisole
or with or without leucovorin calcium

- No prior oxaliplatin

- No prior systemic chemotherapy for metastatic disease

- No prior chemoembolization for metastatic disease

- No prior hepatic artery infusion chemotherapy for metastatic disease

- No other concurrent chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- At least 12 months since prior adjuvant radiotherapy

- Prior radiofrequency ablation allowed

- No prior radiotherapy to the liver

- No prior radiotherapy to more than 25% of the bone marrow

- No concurrent radiotherapy

Surgery

- See Disease Characteristics

- More than 21 days since prior abdominal exploration (with or without intestinal
resection)

Other

- No prior anti-EGFR-directed therapy

- Prior cryotherapy allowed

- No oral cryotherapy on day 1 of each course