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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Reardon, DA; Vredenburgh, JJ; Coan, A; Desjardins, A; Peters, KB; Gururangan, S; Sathornsumetee, S; Rich, JN; Herndon, JE; Friedman, HS

Published Date

  • December 2011

Published In

Volume / Issue

  • 105 / 3

Start / End Page

  • 621 - 627

PubMed ID

  • 21744079

Pubmed Central ID

  • 21744079

Electronic International Standard Serial Number (EISSN)

  • 1573-7373

Digital Object Identifier (DOI)

  • 10.1007/s11060-011-0631-4

Language

  • eng

Conference Location

  • United States