Informace o publikaci

Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study

Autoři	GEISSLER Klaus KORISTEK Zdenek BERNAL del Castillo Teresa NOVAK Jan RODRIGUEZ-MACIAS Gabriela METZELDER Stephan K ILLES Arpad MAYER Jiří ARNAN Montserrat KEATING Mary-Margaret KRAUTER Juergen LUNGHI Monia FRACCHIOLLA Nicola Stefano PLATZBECKER Uwe SANTINI Valeria SANO Yuri OGANESIAN Aram KEER Harold LUEBBERT Michael
Rok publikování	2024
Druh	Článek v odborném periodiku
Časopis / Zdroj	British journal of haematology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://onlinelibrary.wiley.com/doi/10.1111/bjh.19741
Doi	http://dx.doi.org/10.1111/bjh.19741
Klíčová slova	acute myeloid leukaemia; decitabine/cedazuridine; DNA methyltransferase inhibitors; hypomethylating agents; somatic mutations
Popis	This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m(2) for 5-days with orally administered decitabine with cedazuridine (DEC-C), as well as the clinical efficacy and safety of DEC-C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC-IV or oral DEC-C (days 1-5 in a 28-day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC-C for subsequent treatment cycles until treatment discontinuation. Equivalent systemic decitabine exposures were demonstrated (5-day area under the curve ratio between the two decitabine formulations of 99.64 [90% confidence interval 91.23%, 108.80%]). Demethylation rates also were similar (<= 1.1% difference). Median overall survival (OS), clinical response and safety profile with oral DEC-C were consistent with those previously observed with DEC-IV. Next-generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC-C in patients with AML.