Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven or presumptive diagnosis of hepatocellular carcinoma

  • Presumptive diagnosis based on rising alpha-fetoprotein (AFP) levels over 2 assessments, CT scan or MRI of liver, spiral CT scan of portal/splenic vein, and biopsy evidence of cirrhosis
  • Unresectable or recurrent disease after prior surgical resection or embolization therapy
• Fibrolamellar histology allowed if considered surgically unresectable based on tumor size, extrahepatic involvement, or multiple lobe involvement
• CLIP (Cancer of the Liver Italian Program) score less than 4
• Concurrent assignment to a transplantation list allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,200/mm^3
• Platelet count at least 80,000/mm^3

Hepatic:

• Bilirubin no greater than 3.0 mg/dL (except for known Gilbert's Syndrome)
• AST no greater than 5 times upper limit of normal (ULN)
• PT no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No uncontrolled hypertension within the past 3 months
• No unstable angina, symptomatic congestive heart failure, or myocardial infarction within the past 3 months
• No uncontrolled cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active bacterial infections
• HIV negative
• No AIDS
• No other primary malignancy except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer
• No mental incapacitation or psychiatric illness that would preclude study participation
• No other severe disease that would preclude study participation
• Candidate for placement of a central venous access device

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy allowed
• No concurrent biologic therapy

Chemotherapy:

• No prior IV doxorubicin except intraarterial administration in locoregional therapy

Endocrine therapy:

• Prior endocrine therapy allowed
• No concurrent endocrine therapy

Radiotherapy:

• Prior radiotherapy allowed
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Surgery allowed if previously unresectable lesions become resectable
• Recovered from any prior surgery
• No concurrent liver transplantation

Other:

• No other concurrent investigational or marketed anticancer drugs
• No other concurrent therapy for hepatocellular carcinoma
• No concurrent terfenadine, astemizole, or cisapride that may not be interrupted during nolatrexed dihydrochloride administration