title: Brain perfusion and permeability in patients with advanced, refractory glioblastoma treated with lomustine and the transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate.
abstract: Transforming growth factor-β (TGF-β) signaling is associated with tumor progression and vascularization in malignant glioma. In the present study, magnetic resonance imaging was used to evaluate changes in the size and vascularity of glioblastomas in 12 patients who were treated with lomustine and the novel inhibitor of TGF-β signaling, LY2157299 monohydrate. A response in tumor size was observed in 2 of the 12 patients; in 1 of these 2 patients, a reduction in vascular permeability and perfusion was also detected. The effect was observed following 4 cycles of treatment (~3 months). Changes in vascularity have not previously been attributed to treatment with lomustine; therefore, the effect may be associated with LY2157299 treatment. LY2157299 does not appear to have an anti-angiogenic effect when combined with lomustine, and hence may have a different mechanism of action profile compared with anti-angiogenic drugs.
authors.affiliation: Department of Medical Oncology, University Hospital October 12, Madrid 28041, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sepulveda-Sanchez
authors.affiliation: Department of Neuroradiology, University Hospital October 12, Madrid 28041, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos
authors.affiliation: Department of Neuroradiology, University Hospital October 12, Madrid 28041, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Hilario
authors.affiliation: Department of Medical Oncology, University Hospital October 12, Madrid 28041, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: DE Velasco
authors.affiliation: Department of Medical Oncology, University Hospital October 12, Madrid 28041, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia DE LA Torre
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital and The Autonomous University of Barcelona, Barcelona 08999, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Lahn
keywords: combination therapy; glioblastoma; lomustine; magnetic resonance imaging; transforming growth factor-β inhibitor LY2157299