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
- 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
- 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
- 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
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.
Allocation: Randomized, Primary Purpose: Treatment
Nancy E. Kemeny, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|CCOP - Iowa Oncology Research Association||Des Moines, Iowa 50309-1016|
|Penn State Cancer Institute at Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033-0850|
|CCOP - Cedar Rapids Oncology Project||Cedar Rapids, Iowa 52403-1206|
|MBCCOP - University of New Mexico HSC||Albuquerque, New Mexico 87131|
|CCOP - St. Vincent Hospital Cancer Center, Green Bay||Green Bay, Wisconsin 54301|
|Iowa Lutheran Hospital||Des Moines, Iowa 50316-2301|
|John Stoddard Cancer Center at Iowa Methodist Medical Center||Des Moines, Iowa 50309|
|Mercy Cancer Center at Mercy Medical Center-Des Moines||Des Moines, Iowa 50314|
|Midlands Cancer Center at Midlands Community Hospital||Papillion, Nebraska 68128-4157|
|MetroHealth Medical Center||Cleveland, Ohio 44109|