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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/m2/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. [ABSTRACT FROM AUTHOR]

Abstract: For diagnosis and monitoring of Sézary syndrome flow cytometric quantification of CD7− and CD26− T-cells is widely used. Because antigen loss is a characteristic but not disease-specific finding we investigated the significance of this approach. Therefore we analyzed the prevalence of tumor cells in FACS-sorted CD7+/− as well as CD26+/− circulating T-cells applying a clone-specific qualitative and quantitative T-cell receptor PCR. Tumor cells varied considerably in the CD7+ and CD7− cell subset but were largely confined to the CD26− population. We conclude that quantification of CD26− T-cells reflects the tumor cell amount more accurate and should be preferred in the clinical setting. [Copyright &y& Elsevier]