Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01-08) Journal Article

Authors: Wen, P. Y.; Yung, W. K. A.; Lamborn, K. R.; Norden, A. D.; Cloughesy, T. F.; Abrey, L. E.; Fine, H. A.; Chang, S. M.; Robins, H. I.; Fink, K.; Deangelis, L. M.; Mehta, M.; Di Tomaso, E.; Drappatz, J.; Kesari, S.; Ligon, K. L.; Aldape, K.; Jain, R. K.; Stiles, C. D.; Egorin, M. J.; Prados, M. D.
Article Title: Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01-08)
Abstract: Platelet-derived growth factor (PDGF) and its receptors (PDGFR) are frequently coexpressed in meningiomas, potentially contributing to their pathogenesis. The North American Brain Tumor Consortium conducted a phase II study to evaluate the therapeutic potential of imatinib mesylate (Gleevec), a PDGFR inhibitor, in patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical (WHO grade II) and malignant (WHO grade III) meningiomas. The primary end point was 6-month progression-free survival (6M-PFS). Patients requiring enzyme-inducing antiepileptic drugs were ineligible. Patients received imatinib at a dose of 600 mg/day for the first 4-week cycle and then gradually increased to 800 mg/day for subsequent cycles, if there were no unacceptable toxicities. Plasma concentrations of imatinib and its active metabolite, CGP74588, were assessed. Twenty-three heavily pre-treated patients were enrolled into the study (13 benign, 5 atypical, and 5 malignant meningiomas), of whom 22 were eligible. The study was closed prematurely due to slow accrual. Tissue was available only from a minority of patients, but in these specimens there was uniform distribution of PDGFR, the drug target. Imatinib was generally well tolerated. Of 19 patients evaluable for response, 10 progressed at the first scan, and 9 were stable. There were no complete or partial responses. Overall median PFS was 2 months (range, 0.7-34 months); 6M-PFS was 29.4%. For benign meningiomas, median PFS was 3 months (range, 1.1-34 months); 6M-PFS was 45%. For atypical and malignant meningiomas, median PFS was 2 months (range, 0.7-3.7 months); 6M-PFS was 0%. Cycle 1 trough concentrations of imatinib and CGP74588 were 2,129 6 1,600 ng/ml and 517 6 326 ng/ml, respectively. Single-agent imatinib was well tolerated but had no significant activity in recurrent meningiomas. Trough plasma concentrations of imatinib exceeded those associated with imatinib activity in chronic myelogenous leukemia. Copyright 2009 by the Society for Neuro-Oncology.
Keywords: adult; cancer survival; clinical article; treatment outcome; aged; middle aged; survival rate; clinical trial; neutropenia; cancer growth; hypophosphatemia; side effect; antineoplastic agents; neoplasm staging; imatinib; receptor, platelet-derived growth factor alpha; multiple cycle treatment; neoplasm recurrence, local; anemia; leukopenia; dehydration; platelet derived growth factor receptor; pyrimidines; alanine aminotransferase blood level; dizziness; immunoenzyme techniques; tissue distribution; meningeal neoplasms; recurrent disease; protein-tyrosine kinases; meningioma; drug blood level; piperazines; drug dose increase; health care organization; brain hemorrhage; toxicities; north america; pharmacokinetics; 2 [2 methyl 5 [4 (1 piperazinylmethyl)benzamido]anilino] 4 (3 pyridyl)pyrimidine; receptor, platelet-derived growth factor beta
Journal Title: Neuro-Oncology
Volume: 11
Issue: 6
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2009-12-01
Start Page: 853
End Page: 860
Language: English
DOI: 10.1215/15228517-2009-010
PUBMED: 19293394
PROVIDER: scopus
PMCID: PMC2802405
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: NEURJ" - "Source: Scopus"
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MSK Authors
  1. Lauren E Abrey
    276 Abrey