Tipifarnib in acute myeloid leukemia

Treatment of older patients with acute myeloid leukemia (AML) represents a significant challenge. There is little evidence that outcomes are improving for patients subjected to conventional intensive treatment. In addition, there is a large population of patients who are not considered fit for a more intensive treatment approach, and treatment options are limited for these patients. As molecular mechanisms and characteristics of the disease become clearer, they represent potential targets for therapy. One such mechanism is the process of farnesylation, which is required for the activation of RAS proteins and potentially other deranged pathways. The first farnesyltransferase inhibitor (FTI) to undergo assessment in AML is tipifarnib, which has achieved a complete remission in 4% of patients who have relapsed and in 15% of untreated elderly patients. Responses were not restricted to patients with RAS protein mutations and the treatment was well tolerated in general. Several randomized comparative and combination trials have been set up that will establish the position of tipifarnib in the treatment of AML.