Colorectal Cancer, Metastatic Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, liver metastases
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective for metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of intrahepatic floxuridine, leucovorin, and dexamethasone with that of systemic fluorouracil and leucovorin in treating patients who have unresectable liver metastases from colorectal cancer.
Detailed description
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.
Interventions
DRUGdexamethasone
DRUGfloxuridine
DRUGfluorouracil
DRUGleucovorin calcium
PROCEDURElaparotomy
PROCEDUREconventional surgery
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | Up to 5 years |
| Time to progression | Up to 5 years |
Countries
Australia, Peru, Puerto Rico, United States
Outcome results
None listed