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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 (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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 25, 2006 Accepted November 1, 2006 A phase I/II trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies Susan P. Perrine, Olivier Hermine, Trudy Small, Felipe Suarez, Richard O'Reilly, Farid Boulad, Joyce Fingeroth, Melissa Askin, Arthur Levy, Steven J. Mentzer, Massimo DiNicola, Alessandro M. Gianni, Christoph Klein, Steven Horwitz, and Douglas V. Faller* Cancer Research Center, Boston University School of Medicine, Boston, MA, United States Hospital Necker, Paris, France Memorial-Sloan Kettering, New York, NY, United States Beth Israel-Deaconess Hospital, Boston, MA, United States Yale-New Haven Hospital, New Haven, CT, United States Brigham and Women's Hospital, Boston, MA, United States Instituto Tumori, Milan, Italy Children's Hospital, Medical School Hannover, Germany * Corresponding author; email: dfaller{at}bu.edu. 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 fifteen 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 intra-patient 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 fifteen patients showed significant anti-tumor responses, with four CR and six PR within one treatment cycle. Complications from rapid tumor lysis occurred in three patients. Reversible somnolence or stupor occurred in three 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 biological activity in vivo in EBV(+) lymphoid malignancies which are refractory to other regimens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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