Hepatic Arterial Chemoembolization With Cisplatin or Internal Radiation Therapy in Treating Patients With Advanced Liver Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

Primary

• Compare time to disease progression in patients with unresectable advanced hepatocellular carcinoma treated with cisplatin-based trans-arterial chemoembolization vs hepatic intra-arterial yttrium Y 90 glass microspheres (TheraSphere®).
• Compare the health-related quality of life of patients treated with these regimens.
• Compare the safety of these regimens in these patients.

Secondary

• Compare survival of patients treated with these regimens.
• Compare tumor response by CT scan in patients treated with these regimens.
• Compare treatment-related costs, in terms of cost of therapy and number of hospitalization days, in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to extent of tumor in the liver (< 50% vs ≥ 50%) and presence of portal hypertension (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo trans-arterial chemoembolization comprising intra-arterial (IA) infusion of cisplatin over 30-60 minutes followed by embolization of the hepatic artery (that brings blood to the tumor) on day 1. Treatment repeats every 8-10 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive yttrium Y 90 glass microspheres (TheraSphere®) IA on day 1. Beginning 60 days after the first TheraSphere® treatment, patients may receive additional treatment with TheraSphere® only if follow-up CT scans show progressive disease.

Quality of life is assessed at baseline and then every 3 months thereafter.

After the completion of study treatment, patients are followed at 30 days and then every 2 months for 2 years.

PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Histologically or cytologically confirmed hepatocellular carcinoma (HCC)

• Confined to the liver
• Vascular liver mass in the presence of cirrhosis

• Alpha-fetoprotein level > 500 ng/mL
• Measurable disease

• At least 1 unidimensionally measurable lesion > 20 mm by spiral CT scan
• Unresectable disease, due to tumor size or extent or presence of cirrhosis
• No metastatic disease, including brain metastases

• Locoregional lymph node metastases allowed
• No evidence of potential delivery of > 16.5 miCi (30 Gy absorbed dose) of radiotherapy to the lungs either during the first administration of yttrium Y 90 glass microspheres (TheraSphere®) or on cumulative delivery of radiation to the lungs over multiple treatments*
• No evidence of detectable technetium Tc 99m macroaggregated albumin (Tc-99m MAA) flow to the stomach or duodenum after application of established angiographic techniques to stop the flow* NOTE: *For patients randomized to the TheraSphere® arm only

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC > 2,500/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 60,000/mm^3
• No bleeding diathesis not correctable by usual forms of therapy

Hepatic

• See Disease Characteristics
• Bilirubin < 2.0 mg/dL
• AST and/or ALT ≤ 5 times upper limit of normal
• Hepatitis allowed
• No portal hypertension with hepatofugal flow

Renal

• Creatinine < 2.5 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No severe peripheral vascular disease that would preclude catheterization

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double barrier or hormonal contraception during and for at least 30 days after completion of study treatment
• No ongoing or active infection
• No other uncontrolled illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 1 prior systemic chemotherapy for HCC
• More than 4 weeks since prior IV chemotherapy and recovered
• More than 1 year since prior hepatic arterial cisplatin
• More than 4 months since other prior hepatic arterial chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior external hepatic radiotherapy for HCC

Surgery

• Not specified

Other

• No other concurrent therapy for HCC
• No other concurrent investigational agents