TY - JOUR
T1 - Farnesyltransferase inhibitors
T2 - Novel compounds in development for the treatment of myeloid malignancies
AU - Cortes, Jorge E.
AU - Kurzrock, Razelle
AU - Kantarjian, Hagop M.
PY - 2002/7
Y1 - 2002/7
N2 - The farnesyltransferase inhibitors (FTIs) have been shown in early clinical trials to elicit antitumor actions in a broad range of solid and hematologic malignancies. The mechanism of FTI action involves blockade of farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways involved in proliferation, angiogenesis, or decreased apoptosis. Of the four main classes of FTIs, two orally bioavailable FTIs have advanced farthest in clinical development. ZARNESTRA™ (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) and Sarasar (formerly SCH66336, Schering-Plough, Kenilworth, NJ) have demonstrated biologic and clinical activity in a range of solid tumors, and Zarnestra phase I trials have documented clinical responses in approximately 30% of patients with high-risk leukemias or myelodysplastic syndrome (MDS). The main across-class toxicities associated with the use of FTIs are myelosuppression and fatigue. Certain toxicities, such as the QTc abnormalities associated with L-778,123, do not appear to be class related. As results of phase II trials with FTIs in acute and chronic myeloid leukemias and in MDS become available, clinicians will learn more about the potential role of this class of targeted anticancer drugs-and possibly about the clinical distinctions among members of this class.
AB - The farnesyltransferase inhibitors (FTIs) have been shown in early clinical trials to elicit antitumor actions in a broad range of solid and hematologic malignancies. The mechanism of FTI action involves blockade of farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways involved in proliferation, angiogenesis, or decreased apoptosis. Of the four main classes of FTIs, two orally bioavailable FTIs have advanced farthest in clinical development. ZARNESTRA™ (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) and Sarasar (formerly SCH66336, Schering-Plough, Kenilworth, NJ) have demonstrated biologic and clinical activity in a range of solid tumors, and Zarnestra phase I trials have documented clinical responses in approximately 30% of patients with high-risk leukemias or myelodysplastic syndrome (MDS). The main across-class toxicities associated with the use of FTIs are myelosuppression and fatigue. Certain toxicities, such as the QTc abnormalities associated with L-778,123, do not appear to be class related. As results of phase II trials with FTIs in acute and chronic myeloid leukemias and in MDS become available, clinicians will learn more about the potential role of this class of targeted anticancer drugs-and possibly about the clinical distinctions among members of this class.
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U2 - 10.1053/shem.2002.35984
DO - 10.1053/shem.2002.35984
M3 - Article
C2 - 12214290
AN - SCOPUS:0036655361
SN - 0037-1963
VL - 39
SP - 26
EP - 30
JO - Seminars in Hematology
JF - Seminars in Hematology
IS - 3 SUPPL. 2
ER -