Combination Chemotherapy in Treating Patients With Liver Metastases from Colorectal Cancer

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: Randomizedphase III trial to compare the effectiveness of intrahepaticfloxuridine, leucovorin, and dexamethasone with that of systemicfluorouracil and leucovorin in treating patients who have unresectableliver metastases from colorectal cancer.

Condition:
– Colon Cancer
– Liver metastases
– Rectal Cancer

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: Randomizedphase III trial to compare the effectiveness of intrahepaticfloxuridine, leucovorin, and dexamethasone with that of systemicfluorouracil and leucovorin in treating patients who have unresectableliver metastases from colorectal cancer. Condition: – Colon Cancer- Liver metastases- Rectal CancerStudy Type: InterventionalStudy Design: Treatment Official Title: Phase III Randomized Study of Hepatic Artery Infusion of Floxuridine, Leucovorin Calcium (CF), and Dexamethasone Versus IV Fluorouracil and IV CF in Patients With Hepatic Metastases Secondary to Colorectal Cancer Further Study Details: 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. Arm I: Patients undergo laparotomy for placement of a hepatic artery catheter and then subcutaneous placement of a hepatic artery infusion pump. Patients with unresected primary disease also undergo resection at the time of catheter and pump placement. Beginning within 1-2 weeks after surgery, patients receive floxuridine, dexamethasone, and leucovorin calcium (CF) via continuous hepatic artery infusion on days 1-14. Arm II: Patients receive CF IV and fluorouracil IV on days 1-5. Patients with unresected primary disease undergo resection within 3-4 weeks before initiation of chemotherapy. Treatment for patients on both arms continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life and medical resource utilization are assessed at baseline, every 3 months for 1 year, and then at 18 months.Patients are followed every 3 months.PROJECTED ACCRUAL: Approximately 340 patients (170 per arm) will be accrued for this study within approximately 4.5 years. Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both 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 Performance status:Not specified Life expectancy:Not specified Hematopoietic:Not specified Hepatic:See Disease Characteristics Bilirubin no greater than 2 times normal Renal:Not specified 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 PRIOR CONCURRENT THERAPY: Biologic therapy:Not specified 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 Surgery:See Disease Characteristics [1] Westmead Hospital, Westmead, New South Wales, 2145, Australia; Recruiting Richard Kefford, MD, PhD 61-2-9845-6033 [2] Cancer and Leukemia Group B[3] National Cancer Institute (NCI)[4] Eastern Cooperative Oncology Group