dc.contributor.author
Capper, David
dc.contributor.author
von Deimling, Andreas
dc.contributor.author
Brandes, Alba A.
dc.contributor.author
Carpentier, Antoine F.
dc.contributor.author
Kesari, Santosh
dc.contributor.author
Sepulveda-Sanchez, Juan M. [u.v.m.]
dc.date.accessioned
2018-06-08T10:24:27Z
dc.date.available
2017-08-28T11:53:52.212Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20379
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23682
dc.description.abstract
Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor,
blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of
galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14
days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine
therapy, baseline tumor tissue was evaluated to identify markers associated
with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein)
and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments
included chemokine, cytokine, and T cell subsets alterations. 158 patients
were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39)
and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate
for central pathology review and biomarker work. Isocitrate dehydrogenase
(IDH1) negative glioblastoma patients with baseline pSMAD2+ in cytoplasm had
median overall survival (OS) 9.5 months vs. 6.9 months for patients with no
tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H+ and had
a median OS of 10.4 months compared to 6.9 months for patients with negative
IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher
plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and
reduced tumor CD3+ T cell counts. Compared to the baseline, treatment with
galunisertib monotherapy preserved CD4+ T cell counts, eosinophils,
lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was
associated with better OS with MDC/CCL22 as a prominent prognostic marker.
View Full-Text
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
galunisertib monohydrate (LY2157299)
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Biomarker and Histopathology Evaluation of Patients with Recurrent
Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of
Galunisertib and Lomustine
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Int. J. Mol. Sci. - 18 (2017), 5, Artikel Nr. 995
dcterms.bibliographicCitation.doi
10.3390/ijms18050995
dcterms.bibliographicCitation.url
http://www.mdpi.com/1422-0067/18/5/995
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000027682
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008659
dcterms.accessRights.openaire
open access