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.
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.
Authors: David A Reardon; Andrew D Norden; Annick Desjardins; James J Vredenburgh; James E Herndon; April Coan; John H Sampson; Sridharan Gururangan; Katherine B Peters; Roger E McLendon; Julie A Norfleet; Eric S Lipp; Jan Drappatz; Patrick Y Wen; Henry S Friedman Journal: J Neurooncol Date: 2011-09-22 Impact factor: 4.130
Authors: David M Peereboom; Jeffrey G Supko; Kathryn A Carson; Tracy Batchelor; Surasak Phuphanich; Glenn Lesser; Tom Mikkelsen; Tom Mikkelson; Joy Fisher; Serena Desideri; Xiaoying He; Stuart A Grossman Journal: J Neurooncol Date: 2010-05-07 Impact factor: 4.130
Authors: Victor A Levin; Peter J Tonge; James M Gallo; Marc R Birtwistle; Arvin C Dar; Antonio Iavarone; Patrick J Paddison; Timothy P Heffron; William F Elmquist; Jean E Lachowicz; Ted W Johnson; Forest M White; Joohee Sul; Quentin R Smith; Wang Shen; Jann N Sarkaria; Ramakrishna Samala; Patrick Y Wen; Donald A Berry; Russell C Petter Journal: Neuro Oncol Date: 2015-11 Impact factor: 12.300
Authors: Jana Portnow; Behnam Badie; Susan Markel; An Liu; Massimo D'Apuzzo; Paul Frankel; Rahul Jandial; Timothy W Synold Journal: Eur J Cancer Date: 2013-02-04 Impact factor: 9.162
Authors: Patrick Y Wen; W K Alfred Yung; Kathleen R Lamborn; Andrew D Norden; Timothy F Cloughesy; Lauren E Abrey; Howard A Fine; Susan M Chang; H Ian Robins; Karen Fink; Lisa M Deangelis; Minesh Mehta; Emmanuelle Di Tomaso; Jan Drappatz; Santosh Kesari; Keith L Ligon; Ken Aldape; Rakesh K Jain; Charles D Stiles; Merrill J Egorin; Michael D Prados Journal: Neuro Oncol Date: 2009-12 Impact factor: 12.300