Leucovorin, Fluorouracil, Cetuximab, and Oxaliplatin in Treating Patients With Stage IV Colorectal Cancer and Liver Metastases That Cannot Be Removed by Surgery

OBJECTIVES:

Primary

• Determine the efficacy of this regimen by the measurement of objective response rate (RECIST criteria).

Secondary

• Determine the toxicity of this regimen.
• Evaluate the duration of tumor response.
• Determine the duration and rate of tumor control.
• Determine the rate of secondary resectability of hepatic metastases.
• Evaluate progression-free survival
• Determine rate of progression of the tumor.
• Determine overall survival.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1 hour, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours. Patients also receive oxaliplatin by hepatic arterial infusion over 2 hours. Treatment continues for at least 3 months in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary cancer of the colon or rectum

• Isolated hepatic metastases
• Not amenable to curative resection or requirement for complex and or larger (i.e., > 4 liver segments) liver resection
• Measurable disease (RECIST criteria)
• Original tumor must be (or have been) removed

PATIENT CHARACTERISTICS:

Inclusion criteria

• WHO performance status 0-1
• Life expectancy > 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 times normal
• Bilirubin ≤ 1.5 times upper limit of normal
• Transaminases ≤ 5 times normal
• Not pregnant or nursing
• Fertile patients must use effective contraception

Exclusion criteria

• Contraindication or allergy grade 3-4 to any components of the study drugs
• Peripheral neuropathy
• Intestinal occlusion or subocclusion or prior inflammatory intestinal disease
• Severe cardiac disease including any of the following:

• Symptomatic coronary disease
• Myocardial infarction in the past 6 months
• New York Heart Association grade II-IV cardiac insufficiency
• Severe arrhythmia (even if treated)
• Active or uncontrolled infection
• Other concurrent serious disorder
• Severe uncontrolled medical condition
• Other malignancy within the past 5 years or concurrently except basal cell skin cancer or carcinoma in situ of the cervix
• Study impossible due to psychological, geographical, or social reasons
• Prisoners or patients under guardianship

PRIOR CONCURRENT THERAPY:

Exclusion criteria

• Prior chemotherapy except adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, oxaliplatin, irinotecan hydrochloride, and/or bevacizumab (completed > 6 months ago if oxaliplatin- or irinotecan-based)
• Prior epidermal growth factor (EGF), monoclonal antibody inhibiting transduction of EGF receptor (EGFR), or any other treatment targeting the EGFR
• Other concurrent anticancer immunotherapy, chemotherapy, or hormone therapy
• Participation in another study in the past 30 days