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Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme

Authors :
David A, Reardon
Merrill J, Egorin
Jennifer A, Quinn
Jeremy N, Rich
Sridharan, Gururangan
Idharan, Gururangan
James J, Vredenburgh
Annick, Desjardins
Sith, Sathornsumetee
James M, Provenzale
James E, Herndon
Jeannette M, Dowell
Michael A, Badruddoja
Roger E, McLendon
Theodore F, Lagattuta
Kimberly P, Kicielinski
Gregor, Dresemann
John H, Sampson
Allan H, Friedman
August J, Salvado
Henry S, Friedman
Source :
Journal of Clinical Oncology. 23:9359-9368
Publication Year :
2005
Publisher :
American Society of Clinical Oncology (ASCO), 2005.

Abstract

Purpose We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients and Methods Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Results Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Conclusion Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Details

ISSN :
15277755 and 0732183X
Volume :
23
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi.dedup.....26786e36dbac3be97635dd2369b6ca1d
Full Text :
https://doi.org/10.1200/jco.2005.03.2185