Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

OBJECTIVES:

- Compare the efficacy, toxicity, and cost of hepatic artery infusion of floxuridine,
leucovorin calcium (CF), and dexamethasone vs IV fluorouracil and IV CF after resection
of primary disease in patients with hepatic metastases secondary to colorectal cancer.

- Compare the quality of life of patients treated with these regimens.

- Measure the level of thymidylate synthase present in liver metastases, and correlate
these levels with objective response and survival in patients treated with these
regimens.

- Assess the p53 mutations, and correlate findings with objective response and survival
in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
center, percentage of liver involvement on CT scan or MRI (less than 30% vs 30% to under
70%), prior chemotherapy (none vs adjuvant chemotherapy comprising fluorouracil (5-FU) and
leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV) completed at least 1 year before
study vs adjuvant chemotherapy comprising 5-FU with or without LEV completed at least 6
months before study), and synchronous disease (yes vs no). Patients are randomized to 1 of 2
treatment arms.

DISEASE CHARACTERISTICS:

- Unresectable liver metastases secondary to colorectal cancer

- Less than 70% liver involvement on CT scan or MRI

- Liver biopsy required before study unless 1 of the following conditions are met:

- Carcinoembryonic antigen greater than 30

- 5 or more liver metastases visible on CT scan or MRI

- Greater than 50% to under 70% liver involvement on CT scan or MRI

- Histologically proven primary colorectal cancer that is resected or appears
resectable on CT scan and physical exam

- Documentation of previously resected primaries must be based on pathologic
results of the resected tumor

- Histological documentation of synchronous disease must be based on 1 of the
following:

- Biopsy of primary colorectal tumor before study

- Suspicious lesion on barium enema, colonoscopy, or sigmoidoscopy, and a
liver biopsy positive for adenocarcinoma consistent with the primary
colorectal tumor

- Measurable disease

- Clearly defined liver mass measuring at least 2 cm or at least 3 liver masses on
CT scan or MRI

- No evidence of extrahepatic disease on CT scan and physical exam

- No portal vein occlusion or ascites

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Hepatic:

- Bilirubin no greater than 2 times normal

Other:

- No other malignancy within the past 5 years except inactive nonmelanomatous skin
cancer, carcinoma in situ of the cervix, or grade 1 bladder cancer

- Not pregnant or nursing

- Fertile patients must use effective contraception

Chemotherapy:

- At least 1 year since prior adjuvant chemotherapy comprising fluorouracil (5-FU) and
leucovorin calcium (CF) or 5-FU, CF, and levamisole (LEV)

- At least 6 months since prior adjuvant chemotherapy comprising 5-FU with or without
LEV

- No other prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy:

- No concurrent hormonal therapy except for nondisease-related conditions, e.g.:

- Steroids for adrenal failure

- Insulin for diabetes

- Intermittent dexamethasone as an antiemetic

Radiotherapy:

- No prior radiotherapy to the liver