Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

Autor: Desjardins A; Department of Medicine, Division of Neurology, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Box 3624, Durham, NC 27710, USA. desja002@mc.duke.edu, Quinn JA, Vredenburgh JJ, Sathornsumetee S, Friedman AH, Herndon JE, McLendon RE, Provenzale JM, Rich JN, Sampson JH, Gururangan S, Dowell JM, Salvado A, Friedman HS, Reardon DA
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2007 May; Vol. 83 (1), pp. 53-60. Date of Electronic Publication: 2007 Jan 24.
DOI: 10.1007/s11060-006-9302-2
Abstrakt: Purpose: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG).
Patients and Method: Patients with grade III MG 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 anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate.
Results: Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses.
Conclusion: Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.
Databáze: MEDLINE
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