title: Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma.
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.
authors: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. reard003@mc.duke.edu
authors: David A
authors: DA
authors: Reardon
authors: James J
authors: JJ
authors: Vredenburgh
authors: April
authors: A
authors: Coan
authors: Annick
authors: A
authors: Desjardins
authors: Katherine B
authors: KB
authors: Peters
authors: Sridharan
authors: S
authors: Gururangan
authors: Sith
authors: S
authors: Sathornsumetee
authors: Jeremy N
authors: JN
authors: Rich
authors: James E
authors: JE
authors: Herndon
authors: Henry S
authors: HS
authors: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077146:Irinotecan; D000077210:Sunitinib; D002166:Camptothecin