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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1387-1394.
Prepublished online as a Blood First Edition Paper on November 2, 2006; DOI 10.1182/blood-2006-04-014357.
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CLINICAL TRIALS AND OBSERVATIONS
A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia
Jeffrey E. Lancet1,
Ivana Gojo2,
Jason Gotlib3,
Eric J. Feldman4,
Jacqueline Greer10,
Jane L. Liesveld5,
Laura M. Bruzek6,
Lawrence Morris7,
Youn Park8,
Alex A. Adjei6,
Scott H. Kaufmann6,
Elizabeth Garrett-Mayer10,
Peter L. Greenberg3,
John J. Wright9, and
Judith E. Karp10
1 H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL;
2 Greenebaum Cancer Center, University of Maryland, Baltimore;
3 Division of Hematology, Stanford Cancer Center, CA;
4 Weill Medical College, Cornell University, New York, NY;
5 James P. Wilmot Cancer Center, University of Rochester, NY;
6 Mayo Clinic, Rochester, MN;
7 Blood and Marrow Transplant Group of Georgia, Atlanta;
8 Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ;
9 Investigational Drug Branch/Cancer Therapy Evaluation Program (IDB/CTEP), National Cancer Institute, Bethesda, MD; and
10 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
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 (CR) 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 years or older, and poor performance status correlated negatively with survival. Early death in the absence of progressive disease was rare, and drug-related nonhematologic 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.
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