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 Journal Article


Authors: Cloughesy, T. F.; Wen, P. Y.; Robins, H. I.; Chang, S. M.; Groves, M. D.; Fink, K. L.; Junck, L.; Schiff, D.; Abrey, L.; Gilbert, M. R.; Lieberman, F.; Kuhn, J.; Deangelis, L. M.; Mehta, M.; Raizer, J. J.; Yung, W. K. A.; Aldape, K.; Wright, J.; Lamborn, K. R.; Prados, M. D.
Article Title: 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
Abstract: Purpose A phase 11 study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. 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% Cl, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% Cl, 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 EIAEDs) 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.
Keywords: paclitaxel; therapy; ras; anticonvulsants; advanced; kinase; glioblastoma-multiforme; r115777; farnesyl transferase inhibitor
Journal Title: Journal of Clinical Oncology
Volume: 24
Issue: 22
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2006-08-01
Start Page: 3651
End Page: 3656
Language: English
ACCESSION: WOS:000239443400023
DOI: 10.1200/jco.2006.06.2323
PROVIDER: wos
PUBMED: 16877733
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Jeffrey J Raizer
    22 Raizer
  2. Lauren E Abrey
    276 Abrey