Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas |
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| Authors: | Annick Desjardins Jennifer A. Quinn James J. Vredenburgh Sith Sathornsumetee Allan H. Friedman James E. Herndon Roger E. McLendon James M. Provenzale Jeremy N. Rich John H. Sampson Sridharan Gururangan Jeannette M. Dowell August Salvado Henry S. Friedman David A. Reardon |
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| Affiliation: | (1) 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;(2) Department of Surgery, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA;(3) Department of Radiology, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA;(4) Cancer Center Biostatistics, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA;(5) Department of Pathology, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA;(6) Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA;(7) Novartis Pharmaceuticals, East Hanover, NJ, USA |
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| Abstract: | 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. Supported by National Institutes of Health grant nos. 1-P50-CA108786-01, NS20023 and CA11898 and by grant no. MO1 RR 30 through the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health. |
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| Keywords: | Anaplastic astrocytoma Anaplastic oligodendroglioma Growth factor Imatinib mesylate Malignant glioma Phase II trial Platelet-derived |
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