Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies

DOI PDF 被引用文献9件
  • Jorge Cortes
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Maher Albitar
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Deborah Thomas
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Francis Giles
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Razelle Kurzrock
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Alain Thibault
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Wayne Rackoff
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Charles Koller
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Susan O'Brien
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Guillermo Garcia-Manero
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • Moshe Talpaz
    From the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ.
  • 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.

抄録

<jats:p>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.</jats:p>

収録刊行物

  • Blood

    Blood 101 (5), 1692-1697, 2003-03-01

    American Society of Hematology

被引用文献 (9)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ