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, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1692-1697
Number of pages6
JournalBlood
Volume101
Issue number5
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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tipifarnib
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Transferases
Toxicity
Vascular Endothelial Growth Factor A
Plasmas
Transient analysis
Liver
Primary Myelofibrosis
Skin
Blood
Cells
Fatigue of materials
Multiple Myeloma
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Cortes, J., Albitar, M., Thomas, D., Giles, F., Kurzrock, R., Thibault, A., ... Kantarjian, H. (2003). Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood, 101(5), 1692-1697. https://doi.org/10.1182/blood-2002-07-1973

Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. / Cortes, Jorge; Albitar, Maher; Thomas, Deborah; Giles, Francis; Kurzrock, Razelle; Thibault, Alain; Rackoff, Wayne; Koller, Charles; O'Brien, Susan; Garcia-Manero, Guillermo; Talpaz, Moshe; Kantarjian, Hagop.

In: Blood, Vol. 101, No. 5, 01.03.2003, p. 1692-1697.

Research output: Contribution to journalArticle

Cortes, J, Albitar, M, Thomas, D, Giles, F, Kurzrock, R, Thibault, A, Rackoff, W, Koller, C, O'Brien, S, Garcia-Manero, G, Talpaz, M & Kantarjian, H 2003, 'Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies', Blood, vol. 101, no. 5, pp. 1692-1697. https://doi.org/10.1182/blood-2002-07-1973
Cortes, Jorge ; Albitar, Maher ; Thomas, Deborah ; Giles, Francis ; Kurzrock, Razelle ; Thibault, Alain ; Rackoff, Wayne ; Koller, Charles ; O'Brien, Susan ; Garcia-Manero, Guillermo ; Talpaz, Moshe ; Kantarjian, Hagop. / Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. In: Blood. 2003 ; Vol. 101, No. 5. pp. 1692-1697.
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