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

摘要: 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 evaluate the therapeutic potential of imatinib mesylate (Gleevec), PDGFR inhibitor, patients with recurrent meningiomas. Patients were stratified into benign (WHO grade I) meningiomas or atypical II) malignant III) primary end point was 6-month progression-free survival (6M-PFS). requiring enzyme-inducing antiepileptic drugs ineligible. received at dose 600 mg/day for first 4-week cycle then gradually increased 800 subsequent cycles, if there no unacceptable toxicities. Plasma concentrations active metabolite, {"type":"entrez-protein","attrs":{"text":"CGP74588","term_id":"875877231","term_text":"CGP74588"}}CGP74588, assessed. Twenty-three heavily pre-treated enrolled (13 benign, 5 atypical, meningiomas), whom 22 eligible. closed prematurely due slow accrual. Tissue available only from minority patients, but these specimens uniform distribution PDGFR, drug target. Imatinib generally well tolerated. Of 19 evaluable response, 10 progressed scan, 9 stable. There complete partial responses. Overall median PFS 2 months (range, 0.7–34 months); 6M-PFS 29.4%. For 3 1.1–34 45%. 0.7–3.7 0%. Cycle 1 trough {"type":"entrez-protein","attrs":{"text":"CGP74588","term_id":"875877231","term_text":"CGP74588"}}CGP74588 2,129 ± 1,600 ng/ml 517 326 ng/ml, respectively. Single-agent tolerated had significant activity Trough plasma exceeded those associated chronic myelogenous leukemia.