Publication: Phase i study of sunitinib and irinotecan for patients with recurrent malignant glioma
Issued Date
2011-12-01
Resource Type
ISSN
15737373
0167594X
0167594X
Other identifier(s)
2-s2.0-82955232920
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Neuro-Oncology. Vol.105, No.3 (2011), 621-627
Suggested Citation
David A. Reardon, James J. Vredenburgh, April Coan, Annick Desjardins, Katherine B. Peters, Sridharan Gururangan, Sith Sathornsumetee, Jeremy N. Rich, James E. Herndon, Henry S. Friedman Phase i study of sunitinib and irinotecan for patients with recurrent malignant glioma. Journal of Neuro-Oncology. Vol.105, No.3 (2011), 621-627. doi:10.1007/s11060-011-0631-4 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/11420
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Title
Phase i study of sunitinib and irinotecan for patients with recurrent malignant glioma
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Abstract
We determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the oral vascular endothelial growth factor receptor (VEGFR) inhibitor, sunitinib, when administered with irinotecan among recurrent malignant glioma (MG) patients. For each 42-day cycle, sunitinib was administered once a day for four consecutive weeks followed by a 2 week rest. Irinotecan was administered intravenously every other week. Each agent was alternatively escalated among cohorts of 3-6 patients enrolled at each dose level. Patients on CYP3A-inducing anti-epileptic drugs were not eligible. Twenty-five patients with recurrent MG were enrolled, including 15 (60%) with glioblastoma (GBM) and 10 (40%) with grade 3 MG. Five patients progressed previously on bevacizumab and two had received prior VEGFR tyrosine kinase inhibitor therapy. The MTD was 50 mg of sunitinib combined with 75 mg/m 2 of irinotecan. DLT were primarily hematologic and included grade 4 neutropenia in 3 patients and one patient with grade 4 thrombocytopenia. Non-hematologic DLT included grade 3 mucositis (n = 1) and grade 3 dehydration (n = 1). Progression-free survival (PFS)-6 was 24% and only one patient achieved a radiographic response. The combination of sunitinib and irinotecan was associated with moderate toxicity and limited anti-tumor activity. Further studies with this regimen using the dosing schedules evaluated in this study are not warranted. © 2011 Springer Science+Business Media, LLC.