Doxorubicin and Interleukin-2 in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Doxorubicin and Interleukin-2 in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill
 liver cancer cells.

 PURPOSE: Phase II trial to study the effectiveness of doxorubicin and interleukin- 2 in
 treating patients who have liver cancer that cannot be removed by surgery.
OBJECTIVES: I. Evaluate the immunological response to doxorubicin and protracted recombinant
 interleukin-2 in terms of alterations in hepatocellular carcinoma specific cytotoxic T cells
 detectable in peripheral blood in patients with unresectable hepatocellular carcinoma. II.
 Determine the toxicity of this treatment regimen in this patient population. III. Determine
 the tumor response to this regimen in terms of changes in alpha fetoprotein and tumor size
 measured by CT scan in these patients. IV. Determine the progression free survival and
 overall survival of this patient population treated with this regimen. V. Determine the
 correlation between immunological response, tumor response, progression free survival and
 overall survival in these patients.

 OUTLINE: Patients receive doxorubicin IV over 3-5 minutes on day 1 and recombinant
 interleukin-2 (IL-2) IV continuously beginning on day 5 and continuing until day 57. Patients
 achieving partial or complete clinical response regardless of immunological response and
 patients with stable disease and an immunological response continue on IL-2 therapy
 continuously until day 92. Patients with stable disease and no immunological response receive
 an additional dose of doxorubicin on day 57 and then continue on IL-2 until day 92. Patients
 who are clinically eligible with progressive disease and an immunological response continue
 IL-2 therapy as above. Patients are followed at 2 weeks and then monthly thereafter.

 PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within
 approximately 3 years.
DISEASE CHARACTERISTICS: Histologically proven hepatocellular carcinoma OR Elevation of
 alpha fetoprotein (AFP) (greater than 400 ng/mL) in the presence of a space occupying
 lesion in the liver with known chronic liver disease Lesion must be easily biopsied
 Unresectable disease Bidimensionally measurable disease by radiography OR Evaluable disease
 with elevated AFP Okuda stage I disease Tumor size less than 50% of liver No ascites
 Albumin greater than 3 g/dL Bilirubin less than 2 mg/dL OR Okuda stage II disease Bilirubin
 as in stage I If ascites present, albumin must be greater than 3 g/dL

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
 least 12 weeks Hematopoietic: Hemoglobin at least 9.0 g/dL Neutrophil count at least
 1,500/mm3 Platelet count at least 80,000/mm3 Hepatic: See Disease Characteristics SGOT/SGPT
 no greater than 4 times upper limit of normal Any cause of underlying liver disease
 including hepatitis B or C allowed Renal: Creatinine no greater than 2.0 mg/dL
 Cardiovascular: No poor cardiac function No myocardial infarction within the past 6 months
 No poorly controlled arrhythmia No congestive heart failure LVEF at least 45% by MUGA
 Other: No active hepatic encephalopathy No other active malignancies except curatively
 treated nonmelanoma skin cancer or carcinoma in situ of the cervix HIV negative No
 immunodeficiency Not pregnant or nursing Negative pregnancy test Fertile patients must use
 effective contraception

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 6 weeks since prior immunotherapy,
 including interferon Chemotherapy: No prior systemic or intra arterial doxorubicin At least
 6 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: Not
 specified Surgery: See Disease Characteristics Other: At least 4 weeks since prior
 investigational therapy