Phase i study of sunitinib and irinotecan for patients with recurrent malignant glioma

• Main Authors: 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
• Other Authors: Duke University School of Medicine
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Medicine; Neuroscience
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/11420
• Institution: Mahidol University

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.