Publications [#132236] of James M Provenzale

Papers Published

1. DA Reardon, MJ Egorin, JA Quinn, JN Rich, JN Rich Sr, S Gururangan, I Gururangan, JJ Vredenburgh, A Desjardins, S Sathornsumetee, JM Provenzale, JE Herndon 2nd, JM Dowell, MA Badruddoja, RE McLendon, TF Lagattuta, KP Kicielinski, G Dresemann, JH Sampson, AH Friedman, AJ Salvado, HS Friedman, Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme., Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 23 no. 36 (December, 2005), pp. 9359-68, ISSN 0732-183X [doi]
   (last updated on 2011/07/12)

   Abstract:
   OBJECTIVE: 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). 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. CONCLUSIONS: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

   Keywords:
   Administration, Oral • Adult • Aged • Antineoplastic Agents • Antineoplastic Combined Chemotherapy Protocols • Brain Neoplasms • Disease Progression • Drug Administration Schedule • Female • Glioblastoma • Humans • Hydroxyurea • Male • Middle Aged • Piperazines • Pyrimidines • Survival Analysis • administration & dosage • drug therapy* • pathology • therapeutic use*