phenylbutyrate and valganciclovir in treating patients with relapsed or refractory epstein-barr virus-positive cancer

Conditions: Gastric Cancer; Head and Neck Cancer; Lymphoma; Lymphoproliferative Disorder

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent lymphoepithelioma of the nasopharynx post-transplant lymphoproliferative disorder adult nasal type extranodal nk/t-cell lymphoma recurrent adult hodgkin lymphoma aids-related peripheral/systemic lymphoma aids-related primary cns lymphoma recurrent gastric cancer