OBJECTIVES:

Primary

• Determine the 4.5-month progression-free survival rate in patients with advanced unresectable hepatocellular carcinoma treated with gefitinib.

Secondary

• Determine the response rate (complete and partial), in terms of the effects of this drug on measurable disease and serum alpha-fetoprotein levels, in these patients.
• Determine the overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Correlate epidermal growth factor expression at baseline with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 years from study entry.

PROJECTED ACCRUAL: A total of 23-59 patients will be accrued for this study within 19 months.

DISEASE CHARACTERISTICS:

• Diagnosis of advanced unresectable hepatocellular carcinoma based on 1 of the following criteria:

  • Histologically or cytologically confirmed disease
  • Hepatitis B surface antigen negative and alpha-fetoprotein greater than 400 ng/mL
  • Hepatitis B surface antigen positive and alpha-fetoprotein greater than 4,000 ng/mL

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Outside prior radiotherapy field
• No known brain metastases
• Ineligible for surgical resection or liver transplantation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm^3
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic

• See Disease Characteristics
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 5 times ULN
• PT no greater than 6 seconds over control
• INR no greater than 2.3
• Albumin at least 2.8 g/dL
• No Child Pugh Scale class C cirrhosis

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy requiring therapy except nonmelanoma skin cancer
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to gefitinib
• No psychiatric illness or social situation that would preclude study compliance
• No grade 3 or 4 encephalopathy
• No other concurrent uncontrolled illness
• No ongoing or active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy

  • Prior interferon alfa or interferon beta for hepatitis B or C allowed provided the therapy was completed before the diagnosis of hepatocellular carcinoma
• No prior antiangiogenesis therapy

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• No concurrent dexamethasone
• No concurrent glucocorticoids
• No concurrent progesterone

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior palliative radiotherapy

Surgery

• Not specified

Other

• Prior liver-directed therapy (i.e., radiofrequency ablation, cryoablation, percutaneous ethanol injection, chemo-embolization, hepatic artery embolization, and hepatic artery-infused floxuridine) allowed provided patient has progressive hepatic disease or measurable extrahepatic disease
• No prior epidermal growth factor inhibitor therapy
• No other concurrent investigational or commercial anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent inducers of CYP3A4, including the following:

  • Carbamazepine
  • Ethosuximide
  • Griseofulvin
  • Nafcillin
  • Nelfinavir
  • Nevirapine
  • Oxcarbazepine
  • Phenobarbital
  • Phenylbutazone
  • Phenytoin
  • Primidone
  • Rifabutin
  • Rifampin
  • Rofecoxib
  • Hypericum perforatum (St. John's wort)
  • Sulfadimidine
  • Sulfinpyrazone
  • Troglitazone
  • Efavirenz
  • Modafinil
  • Rifapentine