Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia.

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Karp JE, Lancet JE

Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia.

Biologics. 2008 Sep;2(3):491-500. doi: 10.2147/btt.s3485.

PubMed ID

19707379 [ View in PubMed

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Abstract

Farnesyltransferase inhibitors (FTIs) represent a new class of signal transduction inhibitors that block the processing of cellular polypeptides that have cysteine terminal residues and, by so doing, interdict multiple pathways involved in proliferation and survival of diverse malignant cell types. Tipifarnib is an orally bioavailable, nonpeptidomimetic methylquinolone FTI that has exhibited clinical activity in patients with myeloid malignancies including elderly adults with acute myelogenous leukemia (AML) who are not candidates for traditional cytotoxic chemotherapy, patients with high-risk myelodysplasia, myeloproliferative disorders, and imatinib-resistant chronic myelogenous leukemia. Because of its relatively low toxicity profile, tipifarnib provides an important alternative to traditional cytotoxic approaches for elderly patients who are not likely to tolerate or even benefit from aggressive chemotherapy. In this review, we will focus on the clinical development of tipifarnib for treatment of newly diagnosed AML, both as induction therapy for elderly adults with poor-risk AML and as maintenance therapy following achievement of first complete remission following induction and consolidation therapies for poor-risk AML. As with all other malignancies, the optimal approach is likely to lie in rational combinations of tipifarnib with cytotoxic, biologic and/or immunomodulatory agents with non-cross-resistant mechanisms of action. Gene expression profiling has identified networks of differentially expressed genes and gene combinations capable of predicting response to single agent tipifarnib. The clinical and correlative laboratory trials in progress and under development will provide the critical foundations for defining the optimal roles of tipifarnib and in patients with AMl and other hematologic malignancies.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Tipifarnib	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details