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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2571-2578. Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-01-024703. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-01-024703v1 109/6/2571    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Perrine, S. P. Articles by Faller, D. V. Search for Related Content PubMed PubMed Citation Articles by Perrine, S. P. Articles by Faller, D. V. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus–associated lymphoid malignancies Susan P. Perrine1, Olivier Hermine2, Trudy Small3, Felipe Suarez2, Richard O'Reilly3, Farid Boulad3, Joyce Fingeroth6, Melissa Askin1, Arthur Levy5, Steven J. Mentzer4, Massimo Di Nicola8, Alessandro M. Gianni8, Christoph Klein7, Steven Horwitz3, and Douglas V. Faller1 1 Cancer Research Center, Boston University School of Medicine, Boston, MA; 2 Hospital Necker, Paris, France; 3 Memorial-Sloan Kettering, New York, NY; 4 Brigham and Women's Hospital, Boston, MA; 5 Yale School of Medicine, New Haven, CT; 6 Beth Israel-Deaconess Hospital, Boston, MA; 7 Children's Hospital, Hannover Medical School, Germany; 8 Istituto Tumori Nazionale, Milan, Italy Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type antiviral agents because the viral enzyme target of these antiviral drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently infected B cells. As butyrate has been shown to sensitize EBV+ lymphoma cells in vitro to apoptosis induced by ganciclovir, arginine butyrate in combination with ganciclovir was administered in 15 patients with refractory EBV+ lymphoid malignancies to evaluate the drug combination for toxicity, pharmacokinetics, and clinical responses. Ganciclovir was administered twice daily at standard doses, and arginine butyrate was administered by continuous infusion in an intrapatient dose escalation, from 500 mg/(kg/day) escalating to 2000 mg/(kg/day), as tolerated, for a 21-day cycle. The MTD for arginine butyrate in combination with ganciclovir was established as 1000 mg/(kg/day). Ten of 15 patients showed significant antitumor responses, with 4 CRs and 6 PRs within one treatment cycle. Complications from rapid tumor lysis occurred in 3 patients. Reversible somnolence or stupor occurred in 3 patients at arginine butyrate doses of greater than 1000 mg/(kg/day). The combination of arginine butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biologic activity in vivo in EBV+ lymphoid malignancies which are refractory to other regimens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. E. Heslop How I treat EBV lymphoproliferation Blood, November 5, 2009; 114(19): 4002 - 4008. [Abstract] [Full Text] [PDF] J. I. Cohen, H. Kimura, S. Nakamura, Y.-H. Ko, and E. S. Jaffe Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008 Ann. Onc., September 1, 2009; 20(9): 1472 - 1482. [Abstract] [Full Text] [PDF] R. F. Ambinder Epstein-Barr Virus and Hodgkin Lymphoma Hematology, January 1, 2007; 2007(1): 204 - 209. [Abstract] [Full Text] [PDF]

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