Faculty Collaboration Database

Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood 2003 Mar 01;101(5):1692-7

Date

11/02/2002

Pubmed ID

12411300

DOI

10.1182/blood-2002-07-1973

Scopus ID

2-s2.0-0037372488 (requires institutional sign-in at Scopus site)   215 Citations

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.

Author List

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

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Alkyl and Aryl Transferases
Antineoplastic Agents
Blast Crisis
Drug Administration Schedule
Drug Eruptions
Endothelial Growth Factors
Enzyme Inhibitors
Farnesyltranstransferase
Fatigue
Female
Fibroblast Growth Factor 2
Hepatocyte Growth Factor
Humans
Intercellular Signaling Peptides and Proteins
Interferon-alpha
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Chronic-Phase
Lymphokines
Male
Middle Aged
Multiple Myeloma
Nausea
Neoplasm Proteins
Primary Myelofibrosis
Quinolones
Salvage Therapy
Treatment Outcome
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors