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

RATIONALE: The Epstein Barr virus can cause cancer and lymphoproliferative disorders. Ganciclovir is an antiviral drug that acts against the Epstein Barr virus. Arginine butyrate may make virus cells more sensitive to ganciclovir. Combining ganciclovir and arginine butyrate may kill more Epstein Barr virus cells and tumor cells. PURPOSE: Phase I trial to study the effectiveness of arginine butyrate plus ganciclovir in treating patients who have cancer or lymphoproliferative disorders that are associated with the Epstein Barr virus.

Sex

All

Minimum age

3 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

• BACKGROUNDFaller DV, Mentzer SJ, Perrine SP. Induction of the Epstein-Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr Opin Oncol. 2001 Sep;13(5):360-7. doi: 10.1097/00001622-200109000-00008. PMID 11555713
• BACKGROUNDMentzer SJ, Perrine SP, Faller DV. Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. Transpl Infect Dis. 2001 Sep;3(3):177-85. doi: 10.1034/j.1399-3062.2001.003003177.x. PMID 11493400
• RESULTPerrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007 Mar 15;109(6):2571-8. doi: 10.1182/blood-2006-01-024703. Epub 2006 Nov 21. PMID 17119113
• RESULTMentzer SJ, Fingeroth J, Reilly JJ, Perrine SP, Faller DV. Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr-virus-associated lymphoma. Blood Cells Mol Dis. 1998 Jun;24(2):114-23. doi: 10.1006/bcmd.1998.0178. PMID 9628848