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Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme
- Source :
- Journal of Clinical Oncology. 23:9359-9368
- Publication Year :
- 2005
- Publisher :
- American Society of Clinical Oncology (ASCO), 2005.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....26786e36dbac3be97635dd2369b6ca1d
- Full Text :
- https://doi.org/10.1200/jco.2005.03.2185