RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Giving drugs in different ways may kill more tumor cells.
PURPOSE: This phase II trial is studying how well isolated hepatic perfusion with melphalan
works in treating patients with primary unresectable liver cancer or liver metastases.
- Determine response rate, duration of response, and patterns of recurrence in patients
with primary or metastatic, unresectable cancers of the liver after treatment with
isolated hepatic perfusion with melphalan.
- Determine the disease-free and overall survival of patients treated with this regimen.
OUTLINE: Patients who are otherwise eligible undergo an exploratory laparotomy of the
peritoneal cavity. Patients with peritoneal seeding, unresectable extrahepatic metastases,
or unresectable pathologically-involved lymph nodes outside area of portahepatis do not
receive treatment. Remaining patients receive isolated hepatic perfusion with melphalan.
Liver perfusion proceeds for 1 hour.
Patients are followed at 6 weeks, every 3 months for 2 years, and then every 4 months until
PROJECTED ACCRUAL: A maximum of 67 patients will be accrued for this study.
- Histologically or cytologically proven liver cancer meeting 1 of the following
- Primary unresectable hepatocellular or cholangiocellular carcinoma
- Metastatic cancer to the liver originating from one of the following:
- Intraocular melanoma (closed to accrual as of 10/17/03)
- Islet cell carcinoma
- Adenocarcinoma of the colon or rectum limited to parenchyma of the liver
- No evidence of other unresectable extrahepatic colorectal metastasis
- Other neuroendocrine tumors, such as carcinoid tumors
- Measurable disease
- Any age
- ECOG 0-2
- Not specified
- Platelet count greater than 100,000/mm^3
- Hematocrit greater than 27.0%
- WBC at least 2,500/mm^3
- Bilirubin less than 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)
- PT no greater than 2 seconds above upper limit of normal
- Elevated SGOT and SGPT allowed if not due to hepatitis
- No biopsy-proven cirrhosis or evidence of significant portal hypertension
- No prior or concurrent veno-occlusive disease
- Patients with positive hepatitis B or C surface antigen serology and chronic active
hepatitis are eligible provided there is no evidence of cirrhosis
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance greater than 60 mL/min
- Congestive heart failure allowed if LVEF ≥ 40%
- No chronic obstructive pulmonary disease or other chronic pulmonary disease with
pulmonary function tests less than 50% predicted for age
- Weight greater than 30 kg
- Not pregnant or nursing
- Negative pregnancy test
- No active infection
PRIOR CONCURRENT THERAPY:
- At least 1 month since prior anticancer biologic therapy and recovered
- At least 1 month since prior anticancer chemotherapy and recovered
- Not specified
- At least 1 month since prior anticancer radiotherapy and recovered
- Not specified
- Prior intrahepatic arterial infusion therapy allowed
- No chronic use of anticoagulants
- No concurrent immunosuppressive therapy