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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 (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 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. E Articles by Kantarjian, H. Search for Related Content PubMed PubMed Citation Articles by Cortes, J. E Articles by Kantarjian, H. Social Bookmarking                   What's this? Submitted July 15, 2002 Accepted October 5, 2002 Efficacy of the farnesyl transferase inhibitor, ZARNESTRATM (R115777), in chronic myeloid leukemia and other other hematological malignancies Jorge E 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 Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Titusville, NJ, USA * Corresponding author; email: jcortes{at}mdanderson.org. We investigated the clinical activity of the farnesyl transferase inhibitor (FTI) ZARNESTRA (R115777) in patients with chronic myelogenous leukemia (CML, n=22) in chronic (CP, n=10), accelerated (AP, n=6), or blastic phase (n=6), and patients with myelofibrosis (MF), or multiple myeloma (MM). ZARNESTRA was administered at 600 mg orally twice daily for 4 weeks every 6 weeks. Seven patients with CML (CP n=6, AP n=1) achieved a complete (CHR n=5) or partial (PHR n=2) hematologic response. Four patients had a minor cytogenetic response. Responses were transient with a median duration of 9 weeks (range, 3 to 23 weeks). Two patients discontinued therapy because of toxicity while in CHR. In MF, 2 had a significant decrease in splenomegaly, one had normalization of WBC 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 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 VEGF concentrations prior to treatment compared with those who did not respond. Plasma concentrations decreased significantly during therapy among responders. ZARNESTRA, as administered in this study, showed clinical activity in patients with CML and MF, and possibly MM. The effect on VEGF needs to be further investigated to determine whether this might be a possible mechanism of action of ZARNESTRA. Further investigation with ZARNESTRA with alternative schedules and combinations is warranted. 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. Smith, V. Ironside, et al. 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