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

Autor: Geissler K; Sigmund Freud PrivatUniversität, Wien, Austria., Koristek Z; Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic., Del Castillo TB; Hospital Universitario Central de Asturias, Instituo de Investigación Sanitaria del Principado de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain., Novák J; Department of Haematology, Third Faculty of Medicine, Charles University and Faculty Hospital University, Hospital Královské Vinohrady, Prague, Czech Republic., Rodríguez-Macías G; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Metzelder SK; Philipps University Marburg and University Hospital Gießen and Marburg, Marburg, Germany., Illes A; Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary., Mayer J; Fakultní Nemocnice Brno and Masaryk University, Brno, Czech Republic., Arnan M; Institut Català d'Oncologia-Hospital Duran i Reynals, Barcelona, Spain., Keating MM; Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada., Krauter J; Städtisches Klinikum Braunschweig, Klinik für Hämatologie und Onkologie, Braunschweig, Germany., Lunghi M; Azienda Ospedaliero-Universitaria Maggiore Della Carità Novara, Novara, Italy., Fracchiolla NS; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, SC Ematologia, Milan, Italy., Platzbecker U; Universitätsklinikum Leipzig, Leipzig, Germany., Santini V; MDS Unit, Hematology, AOUC, DMSC, Università degli Studi di Firenze, Firenze, Italy., Sano Y; Taiho Oncology, Inc., Pleasanton, California, USA., Oganesian A; Taiho Oncology, Inc., Pleasanton, California, USA., Keer H; Taiho Oncology, Inc., Pleasanton, California, USA., Lübbert M; Department of Haematology, Oncology, and Stem Cell Transplantation, University of Freiburg Medical Center, University of Freiburg Faculty of Medicine, Freiburg, Germany.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Nov; Vol. 205 (5), pp. 1734-1745. Date of Electronic Publication: 2024 Sep 23.
DOI: 10.1111/bjh.19741
Abstrakt: 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.
(© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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