Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Dummer, R; Beyer, M; Hymes, K; Epping, MT; Bernards, R; Steinhoff, M; Sterry, W; Kerl, H; Heath, K; Ahern, JD; Hardwick, JS; Garcia-Vargas, J; Baumann, K; Rizvi, S; Frankel, SR; Whittaker, SJ; Assaf, C; .
Vorinostat combined with bexarotene for treatment of cutaneous T-cell lymphoma: in vitro and phase I clinical evidence supporting augmentation of retinoic acid receptor/retinoid X receptor activation by histone deacetylase inhibition.
LEUK LYMPHOMA. 2012; 53(8): 1501-1508.
Doi: 10.3109/10428194.2012.656625
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Kerl Helmut
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- Abstract:
- The retinoid X receptor (RXR)-agonist bexarotene and the histone deacetylase inhibitor (HDACI) vorinostat are each established monotherapies for cutaneous T-cell lymphomas (CTCLs). We investigated the combination of HDACI and retinoic acid receptor (RAR)/RXR agonists in vitro and in a phase I, multicenter, open-label, two-part dose-escalation study. The combination of bexarotene with a HDACI in vitro leads to cooperative activation of gene transcription and reduction of cell viability in human tumor cell lines. The primary clinical objective was to determine the maximum tolerated dose (MTD) of bexarotene plus vorinostat in 23 patients with CTCLs. The MTD for part I was established at vorinostat 200 mg/day plus bexarotene 300 mg/m(2)/day. The MTD for part II was not reached. Four patients had an objective response and seven patients experienced pruritus relief. We conclude that concomitant administration of vorinostat and bexarotene is feasible only if lower doses of each drug are administered relative to the product label monotherapy doses.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Antineoplastic Combined Chemotherapy Protocols - therapeutic use
- Cell Line, Tumor -
- Cell Survival -
- Female -
- Histone Deacetylase Inhibitors - pharmacology
- Humans -
- Hydroxamic Acids - administration and dosage
- Lymphoma, T-Cell, Cutaneous - drug therapy
- Male -
- Middle Aged -
- Receptors, Retinoic Acid - metabolism
- Retinoid X Receptors - metabolism
- Tetrahydronaphthalenes - administration and dosage
- Transcription, Genetic -
- Find related publications in this database (Keywords)
- CTCL
- HDAC
- histone deacetylase
- cutaneous T-cell lymphoma
- bexarotene
- vorinostat