Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatic malignancy

  • Unresectable disease
  • Disease predominantly in the parenchyma of the liver

  • One of the following primary tumor histologies:

    • Adenocarcinoma of gastrointestinal or other origin
    • Neuroendocrine tumor (except gastrinoma)
    • Primary hepatic malignancy (e.g., hepatocellular cancer or intra-hepatic cholangiocarcinoma)
    • Cutaneous or ocular melanoma (patients must have received prior regional melphalan therapy)
  • Hepatic metastases from colorectal tumors allowed provided patient has undergone prior first-line chemotherapy, including irinotecan or oxaliplatin

• Limited unresectable extrahepatic disease on preoperative radiological studies allowed if life-limiting component of progressive disease is in the liver

  • Limited extrahepatic disease includes, but is not limited to, the following:

    • Up to 4 pulmonary nodules each < 1 cm in diameter
    • Retroperitoneal lymph nodes each < 3 cm in diameter
    • Less than 10 skin or subcutaneous metastases each < 1 cm in diameter
    • Asymptomatic bone metastases that have been or could be palliatively treated with external beam radiotherapy
    • Resectable solitary metastasis to any site

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 16 and over

Sex

• Male or Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Platelet count ≥ 75,000/mm^3
• Hematocrit > 27%
• Absolute neutrophil count ≥ 1,300/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• PT ≤ 2 seconds of upper limit of normal (ULN)
• AST and ALT ≤ 10 times ULN
• No Childs class B or C cirrhosis
• No portal hypertension by history, endoscopy, or radiologic studies

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• No congestive heart failure
• LVEF ≥ 40%

Pulmonary

• No chronic obstructive pulmonary disease
• FEV_1 ≥ 30% of predicted
• DLCO ≥ 40% of predicted

Immunologic

• No active infection
• No severe allergic reaction to iodine contrast agent that is not controlled by premedication with antihistamines or steroids
• No known hypersensitivity reaction to melphalan or heparin in the presence of a heparin induced thrombocytopenia (HIT) antibody

Other

• Weight > 35 kg
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No documented latex allergy
• No evidence of intracranial abnormalities which would lead to risk for bleeding with anticoagulation (e.g., stroke or active metastasis)
• No evidence of active ulcer disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 1 month since prior biologic therapy and recovered

Chemotherapy

• See Disease Characteristics
• More than 1 month since prior chemotherapy and recovered

Endocrine therapy

• Premenopausal women (i.e., have had a period within the past 12 months) must be willing to undergo hormonal suppression during study treatment

Radiotherapy

• See Disease Characteristics
• More than 1 month since prior radiotherapy and recovered

Surgery

• No prior Whipple resection

Other

• Prior intrahepatic perfusion (with or without arterial infusion with floxuridine) or peripheral hepatic perfusion allowed provided the patient had a radiographic partial response of 3 months' duration after therapy
• No concurrent immunosuppressive drugs
• No concurrent chronic anticoagulation therapy