RATIONALE: The Epstein-Barr virus can cause cancer and lymphoproliferative disorders. Valganciclovir is an antiviral drug that acts against the Epstein-Barr virus. Phenylbutyrate may make cells infected with Epstein-Barr virus more sensitive to valganciclovir. Giving phenylbutyrate together with valganciclovir may block the growth of Epstein-Barr virus-infected cells and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving phenylbutyrate together with valganciclovir works in treating patients with relapsed or refractory Epstein-Barr virus-positive cancer.

OBJECTIVES:

Primary

• Determine the rate of Epstein-Barr virus (EBV) lytic phase activation by BZLF1 expression in patients with relapsed or refractory, EBV-positive malignancies treated with phenylbutyrate.

Secondary

• Determine tumor responses in patients treated with phenylbutyrate followed by valganciclovir.
• Track serum EBV load by quantitative polymerase chain reaction and correlate changes with EBV lytic phase activation/tumor response.

OUTLINE: This is an open-label study.

Patients receive oral phenylbutyrate three times daily on days 1-21 and oral valganciclovir once or twice daily on days 4-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients undergo biopsy on day 3 of course 1. Serum Epstein-Barr virus DNA is analyzed for expression of BZLF1 and LMP2 by quantitative polymerase chain reaction on days 3 and 14 of course 1 and on day 1 of each subsequent course.

After completion of study treatment, patients are followed at 1 and 3 months.

PROJECTED ACCRUAL: A total of 14 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Biopsy-proven Epstein-Barr virus (EBV)-positive malignancy

  • Must have tissue analysis to confirm EBV positivity

    • Archival tissue ≤ 1 year old may be used

• Any of the following malignancies:

  • WHO type II or III nasopharyngeal carcinoma

  • Post-transplant lymphoproliferative disorder

  • Nasal NK/T-cell lymphoma

  • Hodgkin's lymphoma

  • Lymphoepithelioma-variant gastric carcinoma

  • AIDS-related lymphomas

    • Patients with CNS non-Hodgkin's lymphoma must have tumor cells present in the cerebrospinal fluid (and assessable with lumbar puncture)

• Relapsed or refractory disease

  • Must have received and failed all prior potentially curative treatment for disease
  • Eligible only for salvage therapy

• Must have tumor tissue amenable for minimally invasive biopsy (e.g., fine-needle aspiration or bone marrow biopsy)

  • No brain tumors not amenable to biopsy

• CNS metastases allowed provided ≥ 2 weeks since prior radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 3 months

• Absolute granulocyte count ≥ 500/mm³

• Platelet count ≥ 50,000/mm³

• Bilirubin ≤ 1.5 times upper limit of normal

• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min

• Recovered from uncontrolled intercurrent illness, including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia

• Able to take medication orally or by gastrostomy tube

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception prior to, during, and for 90 days after completion of study treatment

• No uncontrolled grade 1 symptomatic diarrhea (i.e., > 3 stools/day)

• No concurrent serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent cerebrospinal fluid drugs allowed
• No concurrent zidovudine for HIV-positive patients