A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver
- Compare the disease-free and overall survival of patients with unresectable colorectal
cancer metastatic to the liver treated with regional and systemic chemotherapy with or
without isolated hepatic perfusion with melphalan.
- Compare the response rate and duration of response in patients treated with these
- Compare the patterns of recurrence (liver vs systemic) in patients treated with these
- Compare the health-related quality of life (QOL) of patients treated with these
- Determine whether baseline QOL correlates with length of survival of patients treated
with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy
for liver metastasis (yes vs no) and percentage of hepatic replacement (less than 25% vs at
least 25%). All patients undergo laparotomy to determine final eligibility. Eligible
patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo hyperthermic isolated hepatic perfusion with melphalan over 60
minutes. Patients then undergo placement of an intrahepatic pump or port. At 6 weeks
post hepatic perfusion, patients receive systemic chemotherapy comprising irinotecan IV
over 90 minutes on day 1 followed by fluorouracil IV over 15 minutes and leucovorin
calcium (CF) IV over 15 minutes on days 1-3. Patients receive local chemotherapy
comprising floxuridine (FUDR) and CF by hepatic arterial infusion (HAI) continuously on
- Arm II: Patients undergo placement of an intrahepatic pump or port at laparotomy. At 7
days post laparotomy, patients receive FUDR and CF by HAI continuously for 14 days.
Beginning 2 weeks after completion of HAI, patients receive systemic and local
chemotherapy as in arm I.
Treatment with combined systemic and local chemotherapy repeats every 35 days for a maximum
of 6 courses. Treatment with local chemotherapy alone repeats every 28 days for a maximum of
6 additional courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, postoperatively, every third course of
chemotherapy, every 3 months for 2 years, and then every 6 months thereafter.
Patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 168 patients (84 per treatment arm) will be accrued for this
study within 54 months.
Allocation: Randomized, Primary Purpose: Treatment
H. Richard Alexander, MD, FACS
NCI - Surgery Branch
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|