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: 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
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 105 Issue 3 Pg. 621-7 (Dec 2011) ISSN: 1573-7373 [Electronic] United States
• PMID: 21744079 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Pyrroles
• Irinotecan
• Sunitinib
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (drug therapy, mortality)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Female
• Glioma (drug therapy, mortality)
• Humans
• Indoles (administration & dosage, adverse effects)
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Pyrroles (administration & dosage, adverse effects)
• Sunitinib
• Young Adult