Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium study

Timothy F. Cloughesy*, Patrick Y. Wen, H. Ian Robins, Susan M. Chang, Morris D. Groves, Karen L. Fink, Larry Junck, David Schiff, Lauren Abrey, Mark R. Gilbert, Frank Lieberman, John Kuhn, Lisa M. DeAngelis, Minesh Mehta, Jeff J. Raizer, W. K Alfred Yung, Ken Aldape, John Wright, Kathleen R. Lamborn, Michael D. Prados

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Purpose: A phase II study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a famesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (ElAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on ElAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG). Patients and Methods: Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety. Results: Two AG patients (9.1 %) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% CI, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% CI, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving ElAEDs) seemed similar in EIAED and non-EIAED subgroups. Conclusion: Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population.

Original languageEnglish (US)
Pages (from-to)3651-3656
Number of pages6
JournalJournal of Clinical Oncology
Volume24
Issue number22
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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