Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver and/or Lung

OBJECTIVES:

Primary

• Determine the tumor response rate in patients with colorectal cancer and hepatic and/or pulmonary metastases treated with cetuximab and FOLFIRI chemotherapy comprising irinotecan hydrochloride, leucovorin calcium, and fluorouracil as first-line therapy.

Secondary

• Determine the rate of resectability in patients treated with this regimen.
• Determine the overall and disease-free survival of patients treated with this regimen.
• Determine the tolerability of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 60-120 minutes on days 1 and 8. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2. Patients with 7/6 or 7/7 genotypes also receive filgrastim (G-CSF) as primary prophylaxis (patients with 6/6 genotypes receive G-CSF as secondary prophylaxis). Treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Within 6 weeks after the completion of cetuximab and FOLFIRI chemotherapy, patients with responding disease undergo surgical resection of visceral metastases.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum
• Must have synchronous or metasynchronous unresectable hepatic metastases

• Less than 8 hepatic metastases
• Less than 6 segments of liver involvement with metastases
• No more than 2 potentially resectable extrahepatic (e.g., pulmonary) metastases
• Patients with visceral metastases that are potentially resectable after chemotherapy (i.e., tumor regression) are eligible
• At least 1 measurable metastasis by CT scan or MRI
• No brain metastases, bone metastases, or carcinomatous meningitis
• No celiac lymph node involvement or peritoneal cancer

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• PT rate > 70%
• Bilirubin < 30 μmol/L
• Creatinine < 130 μmol/L
• Creatinine clearance > 60 mL/min
• Not pregnant or nursing
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No severe unstable angina
• No symptomatic heart failure
• No other concurrent illness

PRIOR CONCURRENT THERAPY:

• At least 3 months since prior adjuvant anticancer chemotherapy
• No concurrent participation in another clinical trial