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: Phase II trial to study the effectiveness of cisplatin and epinephrine administered directly into the tumor in treating patients who have primary liver cancer that cannot be removed during surgery.

OBJECTIVES: I. Evaluate the safety and efficacy of cisplatin-epinephrine injectable gel (Intradose MPI-5010) in patients with unresectable primary hepatocellular carcinoma.

PROTOCOL OUTLINE: This is an open label, two stage, multicenter study.

Patients receive intratumoral treatment with ciplatin-epinephrine (MPI-5010) once weekly, for up to four treatments within a six week period, followed by an evaluation two weeks after last treatment. Immediately after the first course, an optional second course of treatment may be undertaken at the discretion of the investigator.

Patients with a complete response, partial response, and/or an increase in necrosis of at least 30% of total treated tumor volume will be followed monthly for up to 6 months. At the completion of 6 months follow up or following documentation of disease progression or development of new tumors, patients are monitored for survival in an extended follow up period.

All nonresponders at the last 2 week posttreatment evaluation are entered in the extended follow up and monitored monthly for survival.

PROJECTED ACCRUAL: Up to 55 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA: --Disease Characteristics--

• Histologically proven unresectable primary hepatocellular carcinoma; No major vessel involvement; Disease must be confined to the liver (no extrahepatic disease); Patients have no more than 3 tumors, with no tumor exceeding 7 cm in diameter, and the sum total tumor volume less than 200 cm3

--Prior/Concurrent Therapy--

• Biologic therapy: No prior biologic therapy for hepatocellular carcinoma; No concurrent immunomodulating agents
• Chemotherapy: No prior or concurrent chemotherapy for hepatocellular carcinoma; No concurrent cytotoxic agents
• Endocrine therapy: No prior endocrine therapy for hepatocellular carcinoma
• Radiotherapy: No prior radiotherapy for hepatocellular carcinoma
• Surgery: Prior surgical resection of the liver allowed
• Other: No concurrent use of aspirin, nonsteroidal anti-inflammatory agents, anticoagulants including warfarin sodium (Coumadin), and epinephrine containing medications including topical anesthetics such as bupivacaine HCl; No prior investigational agents within 4 weeks of study; No concurrent use of probenecid or thiazides; Concurrent use of analgesics and antiemetics is allowed; Concurrent use of topical and other local anesthetics, locoregional nerve blocks, and systemic agents is allowed

--Patient Characteristics--

• Age: 18 and over
• Performance Status: Karnofsky 40-100%
• Life Expectancy: At least 4 months
• Hematopoietic: Hemoglobin at least 10 g/dL; Platelet count at least 75,000/mm3; Absolute granulocyte count at least 1,000/mm3; PT within 3 seconds of institutional norm
• Hepatic: SGPT no greater than 3 times upper limit of normal (ULN); SGOT no greater than 3 times ULN; Child-Pugh grade A or B; Albumin at least 25 g/L; Bilirubin no greater than 2.98 mg/dL; Absent or easily controlled ascites not requiring routine or intermittent paracentesis; Alkaline phosphatase no greater than 2.5 times ULN
• Renal: Creatinine no greater than 1.3 times ULN OR Creatinine clearance at least 45 mL/min
• Cardiovascular: No coronary artery disease; No New York Heart Association class III or greater cardiac symptoms
• Other: Not pregnant or nursing; No medical or psychiatric condition compromising informed consent; No obesity or tumor location that would limit adequate tumor imaging; No history of bleeding from liver tumor(s) or gastroesophageal bleeding; No known hypersensitivity to cisplatin, bovine collagen, epinephrine, sulfites or radiographic contrast agents; No history of encephalopathy