A Phase II Study Of Hepatic Arterial Infusion Of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) For Unresectable Primary And Metastatic Cancers Of The Liver

Inclusion Criteria

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