A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia

M. H. Kirschbaum, T. Synold, A. S. Stein, Joseph Tuscano, J. M. Zain, L. Popplewell, C. Karanes, M. R. O'Donnell, B. Pulone, A. Rincon, J. Wright, P. Frankel, S. J. Forman, E. M. Newman

Research output: Contribution to journalArticle

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Abstract

Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b.i.d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML.

Original languageEnglish (US)
Pages (from-to)1543-1547
Number of pages5
JournalLeukemia
Volume25
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint

tipifarnib
Myeloid Leukemia
Farnesyltranstransferase
Appointments and Schedules
Acute Myeloid Leukemia
Maximum Tolerated Dose
Leukemia
Pharmacokinetics
Clinical Trials
Kidney
Liver

Keywords

  • acute myelogenous leukemia
  • AML
  • farnesyltransferase
  • phase 1 trial
  • tipifarnib
  • Zarnestra

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia. / Kirschbaum, M. H.; Synold, T.; Stein, A. S.; Tuscano, Joseph; Zain, J. M.; Popplewell, L.; Karanes, C.; O'Donnell, M. R.; Pulone, B.; Rincon, A.; Wright, J.; Frankel, P.; Forman, S. J.; Newman, E. M.

In: Leukemia, Vol. 25, No. 10, 10.2011, p. 1543-1547.

Research output: Contribution to journalArticle

Kirschbaum, MH, Synold, T, Stein, AS, Tuscano, J, Zain, JM, Popplewell, L, Karanes, C, O'Donnell, MR, Pulone, B, Rincon, A, Wright, J, Frankel, P, Forman, SJ & Newman, EM 2011, 'A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia', Leukemia, vol. 25, no. 10, pp. 1543-1547. https://doi.org/10.1038/leu.2011.124
Kirschbaum, M. H. ; Synold, T. ; Stein, A. S. ; Tuscano, Joseph ; Zain, J. M. ; Popplewell, L. ; Karanes, C. ; O'Donnell, M. R. ; Pulone, B. ; Rincon, A. ; Wright, J. ; Frankel, P. ; Forman, S. J. ; Newman, E. M. / A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia. In: Leukemia. 2011 ; Vol. 25, No. 10. pp. 1543-1547.
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