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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-1973. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-1973v1 101/5/1692    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 Cortes, J. Articles by Kantarjian, H. Search for Related Content PubMed PubMed Citation Articles by Cortes, J. Articles by Kantarjian, H. Related Collections Neoplasia Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1692-1697 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies Jorge Cortes, Maher Albitar, Deborah Thomas, Francis Giles, Razelle Kurzrock, Alain Thibault, Wayne Rackoff, Charles Koller, Susan O'Brien, Guillermo Garcia-Manero, Moshe Talpaz, and Hagop Kantarjian From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ. We investigated the clinical activity of the farnesyl transferase inhibitor R115777 in 22 patients with chronic myelogenous leukemia (CML) in chronic, accelerated, or blastic phase and in 8 patients with myelofibrosis (MF) and 10 patients with multiple myeloma (MM). R115777 was administered at 600 mg orally twice daily for 4 weeks every 6 weeks. Seven patients with CML (6 in chronic phase, 1 in advanced phase) achieved complete or partial hematologic response. Four of them had a minor cytogenetic response. Responses were transient, with a median duration of 9 weeks (range, 3-23 weeks). Two patients discontinued therapy because of toxicity while in complete hematologic response. Two MF patients had a significant decrease in splenomegaly, one had normalization of white blood cell count and differential, and one became transfusion independent. One patient with MM had a reduction in monoclonal protein of 34%. Adverse events included nausea in 22 patients (55%; all grade 2 or lower) and fatigue in 19 (48%; grade 3 or higher in 1). Other grade 3 or 4 toxicities included skin rash (4 patients, 10%), peripheral neuropathy (2 patients, 5%), and liver toxicity (2 patients, 5%). Patients who responded to therapy had significantly higher plasma vascular endothelial growth factor (VEGF) concentrations prior to treatment than nonresponders. Plasma concentrations decreased significantly during therapy among responders. R115777 showed clinical activity in patients with CML and MF. The effect on VEGF needs to be further investigated to determine whether this might be a possible mechanism of action of R115777. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. E. Karp, K. Flatten, E. J. Feldman, J. M. Greer, D. A. Loegering, R. M. Ricklis, L. E. Morris, E. Ritchie, B. D. 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