Tipifarnib in the treatment of acute myeloid leukemia

Farnesyltransferase inhibitors (FTIs) are a new class of biologically active anticancer drugs. The exact anti-tumorigenic mechanism is currently unknown. FTIs inhibit farnesylation of a wide range of target proteins. In preclinical models, tipifarnib (R115777, Zarnestra®), a non-peptidomimetic competitive FTI, showed great potency against leukemic cells. Although it has recently demonstrated clinical responses in adults with refractory and relapsed acute myeloid leukemia (AML), and in older adults with newly diagnosed poor-risk AML, its activity was far less than anticipated. However, it appears that tipifarnib as a single agent may be important in selected groups of patients. Much remains to be learned to optimize such therapy in patients with AML. To this end, trials that combine tipifarnib with cytotoxics are ongoing.