Isolated Hepatic Perfusion With Melphalan in Treating Patients With Unresectable Colorectal Cancer That Has Metastasized to the Liver
Isolated Hepatic Perfusion With Melphalan in Treating Patients With Unresectable Colorectal Cancer That Has Metastasized to the Liver
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop
 tumor cells from dividing so they stop growing or die. Giving chemotherapy 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 unresectable colorectal cancer that has metastasized to the
 liver.
OBJECTIVES:

 Primary

 -  Determine the response and duration of response in patients with unresectable colorectal
 cancer metastatic to the liver and refractory to first-line systemic chemotherapy
 treated with isolated hepatic perfusion with melphalan.

 Secondary

 -  Determine the pattern of recurrence (liver vs systemic) in patients treated with this
 regimen.

 -  Determine hepatic progression-free and overall survival in patients treated with this
 regimen.

 -  Determine the time to hepatic and systemic progression in patients treated with this
 regimen.

 -  Determine quality of life (QOL) in patients treated with this regimen.

 -  Correlate baseline QOL with length of survival in patients treated with this regimen.

 OUTLINE: Patients undergo a limited laparotomy to determine if extrahepatic disease that was
 not visualized during preoperative scanning is present. Patients found to have peritoneal
 seeding or unresectable extrahepatic metastatic disease not previously visualized on scans do
 not receive isolated hepatic perfusion (IHP). Remaining patients undergo IHP with melphalan
 and hyperthermia therapy. Liver perfusion continues for 1 hour.

 Quality of life is assessed at baseline, 6 weeks, and then every 3-4 months for 3 years.

 Patients are followed at 6 weeks, every 3-4 months for 3 years, and then every 6 months
 thereafter.

 PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically confirmed colorectal cancer

 -  Metastatic disease limited to the parenchyma of the liver

 -  Patients with limited sites of extrahepatic disease AND who have dominant
 life-limiting disease in the liver are considered eligible provided the
 extrahepatic sites can be treated with local ablative measures (e.g.,
 resection or external beam radiotherapy)

 -  No other evidence of unresectable extrahepatic disease by radiological
 studies

 -  Unresectable hepatic disease defined by > 3 sites of disease in the liver, bilobar
 disease, or tumor abutting major vascular or ductal structures making anatomic
 resection with liver function preservation impossible

 -  Measurable disease

 -  Refractory to prior first-line systemic chemotherapy

 -  Disease progression during or after completion of treatment with an irinotecan-
 or oxaliplatin-containing regimen for established hepatic metastases

 -  Treatment failure is defined as disease progression evidenced by tumor
 growth OR new lesions on imaging modalities OR increasing carcinoembryonic
 antigen (CEA)

 PATIENT CHARACTERISTICS:

 Age

 -  18 and over

 Performance status

 -  ECOG 0-2

 Life expectancy

 -  Not specified

 Hematopoietic

 -  Hematocrit > 27.0%

 -  Platelet count > 100,000/mm^3

 -  WBC > 3,000/mm^3

 Hepatic

 -  Bilirubin < 2.0 mg/dL

 -  PT ≤ 2 seconds of the upper limit of normal

 -  ALT and AST elevations secondary to metastatic disease allowed

 -  Chronic active hepatitis B or C allowed provided there is no evidence of cirrhosis on
 pathology, radiologic studies, or physical exam

 -  No history of veno-occlusive disease

 -  No biopsy proven cirrhosis

 -  No evidence of significant portal hypertension manifested by ascites, esophageal
 varices on endoscopy, or radiologic studies showing significant collateral vessels
 around the organs drained by the portal venous system

 -  No other liver condition that would preclude study therapy

 Renal

 -  Creatinine ≤ 1.5 mg/dL OR

 -  Creatinine clearance > 60 mL/min

 Cardiovascular

 -  LVEF ≥ 40%

 -  No ischemic cardiac disease

 -  No history of congestive heart failure

 Pulmonary

 -  Chronic obstructive pulmonary disease or other chronic pulmonary disease allowed
 provided pulmonary function test ≥ 50% of predicted

 Other

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  No active infection

 -  Weight > 30 kg

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  More than 4 weeks since prior biologic therapy for the malignancy and recovered

 Chemotherapy

 -  See Disease Characteristics

 -  More than 4 weeks since prior chemotherapy for the malignancy and recovered

 Endocrine therapy

 -  Not specified

 Radiotherapy

 -  See Disease Characteristics

 -  More than 4 weeks since prior radiotherapy for the malignancy and recovered

 Surgery

 -  See Disease Characteristics

 Other

 -  No concurrent immunosuppressive drugs

 -  No concurrent chronic anticoagulation therapy