title: Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma.
abstract: Tyrosine kinase signaling through the vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor- α (PDGFR-α) and KIT cell surface receptors mediates neo-angiogenesis and contributes to cancer cell survival in recurrent anaplastic and low-grade glioma. Thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma were treated with sunitinib malate, a small-molecule tyrosine kinase inhibitor of the VEGFR, PDGFR, and KIT receptors, in combination with lomustine. The most frequent grade 3 and 4 adverse events were fatigue, thrombocytopenia, neutropenia and lymphopenia. The best objective tumor response by Response Assessment in Neuro-Oncology (RANO) criteria was one complete response, one unconfirmed partial response and three cases of stable disease. The median progression-free survival was 1.8 months (95% confidence interval=1.0-2.7 months) with 6-month progression-free survival of 15% (95% confidence interval=0-35%). The median overall survival was 6.7 months (95% confidence interval=0.7-12 months). The investigated combination regimen of sunitinib and lomustine is well-tolerated but insufficiently active to warrant further investigation in an unselected population of patients with temozolomide-refractory recurrent anaplastic and low-grade glioma.
authors.affiliation: Department of Neurosurgery,Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Johnny
authors.initials: J
authors.lastname: Duerinck
authors.affiliation: Department of Neurosurgery,Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Du Four
authors.affiliation: NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Sander
authors.affiliation: Department of Radiology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Van Binst
authors.affiliation: Department of Nuclear Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Everaert
authors.affiliation: Department of Neuropathology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Alex
authors.initials: A
authors.lastname: Michotte
authors.affiliation: NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany Department of Oncology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium bart.neyns@uzbrussel.be.
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007211:Indoles; D011758:Pyrroles; D008130:Lomustine; D003606:Dacarbazine; D000077210:Sunitinib; D000077204:Temozolomide
keywords: Sunitinib; glioma; lomustine; recurrent disease