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