Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme
| Autor: | David A, Reardon, Merrill J, Egorin, Jennifer A, Quinn, Jeremy N, Rich, Sridharan, Gururangan, Idharan, Gururangan, James J, Vredenburgh, Annick, Desjardins, Sith, Sathornsumetee, James M, Provenzale, James E, Herndon, Jeannette M, Dowell, Michael A, Badruddoja, Roger E, McLendon, Theodore F, Lagattuta, Kimberly P, Kicielinski, Gregor, Dresemann, John H, Sampson, Allan H, Friedman, August J, Salvado, Henry S, Friedman |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty medicine.drug_class medicine.medical_treatment Administration Oral Phases of clinical research Antineoplastic Agents Gastroenterology Drug Administration Schedule Piperazines Tyrosine-kinase inhibitor Hydroxycarbamide Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Hydroxyurea Aged Chemotherapy Temozolomide Brain Neoplasms business.industry Imatinib Middle Aged medicine.disease Survival Analysis Surgery Pyrimidines Imatinib mesylate Oncology Benzamides Disease Progression Imatinib Mesylate Female Glioblastoma business Progressive disease medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 23:9359-9368 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2005.03.2185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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