Ganciclovir Plus Arginine Butyrate in Treating Patients With Cancer or Lymphoproliferative Disorders Associated With the Epstein Barr Virus

OBJECTIVES:

• Determine the safety, toxicity, and the reversibility of toxicity of arginine butyrate in patients with Epstein Barr virus-induced malignancies or lymphoproliferative disorders.
• Determine the clinical pharmacology of arginine butyrate when administered with ganciclovir, including plasma half life and major routes of elimination in these patients.
• Determine the biologic effects of arginine butyrate in terms of inducing sensitivity to ganciclovir in tissue samples from selected patients.
• Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: Patients receive ganciclovir IV over 1 hour twice a day on days -1 to 21 for the first course (days 0-21 for all subsequent courses) and escalating doses of arginine butyrate IV continuously on days 0-21. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for a minimum of 42 days.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy or lymphoproliferative disease including the following:

• Nasopharyngeal carcinoma
• Hodgkin's lymphoma
• African Burkitt's lymphoma
• T-cell non-Hodgkin's lymphoma
• B-cell non-Hodgkin's lymphoma if Epstein Barr Virus (EBV) positive
• Other lymphomas associated with immunodeficiency or immunosuppression, including AIDS-related lymphoma
• B-cell lymphoproliferative disorders
• Monoclonal or oligoclonal B-cell lymphoid disease (no polyclonal disease)
• EBV positive by immunohistochemistry or in situ hybridization

• Negative serology for EBV allowed

PATIENT CHARACTERISTICS:

Age:

• 3 and over

Performance status:

• Any status

Hematopoietic:

• Absolute granulocyte count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Aminotransferase less than 2 times normal

Renal:

• Creatinine less than 3.0 mg/dL
• Creatinine clearance greater than 30 mL/min

Cardiovascular:

• No acute myocardial infarction within the past 6 months
• No atrial fibrillation within the past 6 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior bone marrow or stem cell transplantation allowed
• No concurrent immunotherapy
• No concurrent interferon or tacrolimus

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• Recovered from prior radiotherapy

Surgery:

• Not specified