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Cancer Chemotherapy and Pharmacology

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01-06-2012 | Original Article

Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study

Authors: Robert S. Jansen, Hilde Rosing, Pierre W. Wijermans, Ron J. Keizer, Jan H. M. Schellens, Jos H. Beijnen

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2012

Abstract

Purpose

Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients.

Method

This article describes a method for the quantitative determination of decitabine triphosphate in PBMCs using liquid chromatography coupled to tandem mass spectrometry. The method was applied to ex vivo incubated whole blood samples and samples from three patients receiving prolonged low-dose decitabine treatment.

Results

We successfully quantitated decitabine triphosphate in PBMCs. Considerable levels were detected in PBMCs from two patients that responded well to therapy, whereas only low levels were present in a non-responding patient. Moreover, the data show that, in contrast to plasma decitabine, intracellular decitabine triphosphate accumulates during a treatment cycle of nine infusions at a dose of 15 mg/m².

Conclusions

The results suggest a relationship between decitabine triphosphate levels and response to therapy. Based on the observed accumulation of decitabine triphosphate during a treatment cycle, a less intensive dose scheme could be feasible.

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Title: Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study
Authors: Robert S. Jansen
Hilde Rosing
Pierre W. Wijermans
Ron J. Keizer
Jan H. M. Schellens
Jos H. Beijnen
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1850-x

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