Impact of pharmacokinetics on the toxicity and efficacy of clofarabine in patients with relapsed or refractory acute myeloid leukemia

Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukem...

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Hauptverfasser: Büttner, Božena (VerfasserIn) , Knoth, Holger (VerfasserIn) , Kramer, Michael (VerfasserIn) , Oertel, Reinhard (VerfasserIn) , Seeling, Andreas (VerfasserIn) , Sockel, Katja (VerfasserIn) , von Bonin, Malte (VerfasserIn) , Stölzel, Friedrich (VerfasserIn) , Alakel, Nael (VerfasserIn) , Platzbecker, Uwe (VerfasserIn) , Röllig, Christoph (VerfasserIn) , Ehninger, Gerhard (VerfasserIn) , Bornhäuser, Martin (VerfasserIn) , Schetelig, Johannes (VerfasserIn) , Middeke, Jan Moritz (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 16 May 2017
In: Leukemia and lymphoma
Year: 2017, Jahrgang: 58, Heft: 12, Pages: 2865-2874
ISSN:1029-2403
DOI:10.1080/10428194.2017.1319051
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/10428194.2017.1319051
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Verfasserangaben:Bozena Büttner, Holger Knoth, Michael Kramer, Reinhard Oertel, Andreas Seeling, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Nael Alakel, Uwe Platzbecker, Christoph Röllig, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig & Jan Moritz Middeke

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520 |a Common side effects of clofarabine (CFB) are liver toxicity, particularly a transient elevation of transaminases and skin toxicity. We studied the correlation of pharmacokinetic (PK) parameters with these toxicities and the efficacy of CFB in patients with relapsed or refractory acute myeloid leukemia. Clofarabine PK parameters showed large inter-individual variability. A higher CFB area under the curve was significantly associated with higher transaminase levels (p = .011 for aspartate aminotransferase (AST), adjusted for age, sex, cumulated CFB dosage, baseline AST, and glomerular filtration rate (GFR)). No significant association could be found between maximum concentration and the liver toxicity parameters. The occurrence of skin toxicity and the response to re-induction chemotherapy evaluated at day 15 were also not associated with PK. In conclusion, a higher individual CFB exposure is associated with increased liver toxicity reflected by elevated liver enzymes, without having an impact on anti-leukemic efficacy. 
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