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 and giving them in different ways
may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of melphalan given as an isolated hepatic
perfusion followed by chemotherapy infused into the liver in patients who have unresectable
colorectal cancer that is metastatic to the liver.
OBJECTIVES: I. Determine the response rate and response duration in patients with
unresectable colorectal cancer metastatic to the liver treated with isolated hepatic
perfusion with melphalan followed by postoperative hepatic arterial chemotherapy.
II. Determine the patterns of recurrence in this patient population with this treatment
III. Evaluate the disease-free survival and overall survival in these patients.
IV. Evaluate health related quality of life and determine whether baseline correlates with
the length of survival.
PROTOCOL OUTLINE: Patients undergo surgery and hyperthermic isolated hepatic perfusion with
melphalan given intra-arterially over 60 minutes.
At six weeks post-hepatic perfusion, patients receive floxuridine and leucovorin calcium
intra-arterially as a continuous infusion over 14 days. Treatment repeats every 28 days in
the absence of disease progression or unacceptable toxicity.
Quality of life is assessed prior to study and then at each followup visit. Patients are
followed every 3-4 months for 3 years and then every 6 months thereafter or until disease
A total of 50 patients will be accrued for this study.
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics-- Histologically or cytologically proven measurable metastatic
colorectal cancer limited to the parenchyma of the liver No evidence of unresectable
extrahepatic disease Limited resectable extrahepatic disease allowed Unresectable liver
disease defined as: Greater than 3 sites of liver disease OR Bilobar disease OR Tumor
abutting major vascular or ductal structures, impeding resection with preservation of
liver function OR Limited extrahepatic disease No biopsy-proven cirrhosis No significant
portal hypertension --Prior/Concurrent Therapy-- Biologic therapy: At least 4 weeks since
prior biologic therapy for colorectal cancer and recovered Chemotherapy: At least 4 weeks
since prior chemotherapy for colorectal cancer and recovered No prior intrahepatic
arterial infusional therapy using floxuridine Endocrine therapy: Not specified
Radiotherapy: At least 4 weeks since prior radiotherapy for colorectal cancer and
recovered Surgery: See Disease Characteristics Other: No concurrent immunosuppressive
drugs No concurrent chronic anticoagulants --Patient Characteristics-- Age: Not specified
Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Platelet count
greater than 100,000/mm3 Hematocrit greater than 27.0% WBC greater than 3,000/mm3 Hepatic:
Bilirubin less than 2.0 mg/dL PT no greater than 2 seconds over upper limit of normal
Elevated hepatic transaminases secondary to liver metastases allowed No veno-occlusive
disease Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than
60 mL/min Cardiovascular: No congestive heart failure with LVEF less than 40% Pulmonary:
No chronic obstructive pulmonary disease No other chronic pulmonary disease with pulmonary
function test less than 50% predicted Other: No active infections HIV negative Body weight
greater than 30 kg Not pregnant or nursing Negative pregnancy test