Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Reardon, DA; Egorin, MJ; Quinn, JA; Rich, JN; Gururangan, S; Vredenburgh, JJ; Desjardins, A; Sathornsumetee, S; Provenzale, JM; Herndon, JE; Dowell, JM; Badruddoja, MA; McLendon, RE; Lagattuta, TF; Kicielinski, KP; Dresemann, G; Sampson, JH; Friedman, AH; Salvado, AJ; Friedman, HS

Published Date

  • December 20, 2005

Published In

Volume / Issue

  • 23 / 36

Start / End Page

  • 9359 - 9368

PubMed ID

  • 16361636

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.03.2185


  • eng

Conference Location

  • United States