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Acute Myelogenous Leukemia
By admin at 2006-11-09 01:35
Acute Myelogenous Leukemia

A phase II study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia.

Outcomes for older adults with acute myelogenous leukemia (AML) are poor due to both disease and host-related factors. In this phase 2 study, we tested the oral farnesyltransferase inhibitor tipifarnib in 158 older adults with previously untreated, poor-risk AML. The median age was 74 years, and a majority of patients had antecedent myelodysplastic syndrome. Complete remission was achieved in 22 patients (14%); partial remission or hematologic improvement occurred in 15 patients, for an overall response rate of 23%. The median duration of CR was 7.3 months and the median survival of complete responders was 18 months. Adverse karyotype, age >/=75, and poor performance status correlated negatively with survival. Early death in the absence of progressive disease was rare, and drug-related non-hematologic serious adverse events were observed in 74 patients (47%). Inhibition of farnesylation of the surrogate protein HDJ-2 occurred in the large majority of marrow samples tested. Baseline levels of phosphorylated mitogen-activated protein kinase and AKT did not correlate with clinical response. Tipifarnib is active and well tolerated in older adults with poor-risk AML, and may impart a survival advantage in those patients who experience a clinical response.

* Lancet JE,
* Gojo I,
* Gotlib J,
* Feldman EJ,
* Greer J,
* Liesveld JL,
* Bruzek LM,
* Morris L,
* Park Y,
* Adjei AA,
* Kaufmann SH,
* Garrett-Mayer E,
* Greenberg PL,
* Wright JJ,
* Karp JE.



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