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