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: 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.
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: conventional surgery
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||PHASE III STUDY OF HEPATIC ARTERY FLOXURIDINE (FUDR), LEUCOVORIN (LV), AND DEXAMETHASONE (DEX) VERSUS SYSTEMIC 5-FLUOROURACIL (5-FU) AND LEUCOVORIN (LV) AS TREATMENT FOR HEPATIC METASTASES FROM COLORECTAL CANCER|
|Study Start Date:||January 1996|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002716
|United States, Iowa|
|CCOP - Cedar Rapids Oncology Project|
|Cedar Rapids, Iowa, United States, 52403-1206|
|CCOP - Iowa Oncology Research Association|
|Des Moines, Iowa, United States, 50309-1016|
|Iowa Lutheran Hospital|
|Des Moines, Iowa, United States, 50316-2301|
|John Stoddard Cancer Center at Iowa Methodist Medical Center|
|Des Moines, Iowa, United States, 50309|
|Mercy Cancer Center at Mercy Medical Center-Des Moines|
|Des Moines, Iowa, United States, 50314|
|United States, Nebraska|
|Midlands Cancer Center at Midlands Community Hospital|
|Papillion, Nebraska, United States, 68128-4157|
|United States, New Mexico|
|MBCCOP - University of New Mexico HSC|
|Albuquerque, New Mexico, United States, 87131|
|United States, Ohio|
|MetroHealth Medical Center|
|Cleveland, Ohio, United States, 44109|
|United States, Pennsylvania|
|Penn State Cancer Institute at Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|United States, Wisconsin|
|CCOP - St. Vincent Hospital Cancer Center, Green Bay|
|Green Bay, Wisconsin, United States, 54307-3453|
|Australia, New South Wales|
|Westmead, New South Wales, Australia, 2145|
|Instituto de Enfermedades Neoplasicas|
|Lima, Peru, 34|
|San Juan City Hospital|
|San Juan, Puerto Rico, 00936-7344|
|Study Chair:||Nancy E. Kemeny, MD||Memorial Sloan-Kettering Cancer Center|
|Study Chair:||Elin Ruth Sigurdson, MD||Fox Chase Cancer Center|