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

This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m<sup>2</sup> 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.

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Publication Details

Journal
British Journal of Haematology
Published
2024-09-23
DOI
https://doi.org/10.1111/bjh.19741
Citations
17
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
7.72

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article

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

Aram Oganesian, Mary‐Margaret Keating, Gabriela Rodríguez‐Macías, Árpád Illés et al.
17 citations
British Journal of Haematology
Acute Myeloid Leukemia Research
7.72
article

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

Aram Oganesian, Mary‐Margaret Keating, Gabriela Rodríguez‐Macías, Árpád Illés, Stephan Metzelder, Harold Keer, Zdeněk Kořı́stek, Michael Lübbert, Monia Lunghi, Jiřı́ Mayer, Teresa Bernal, Klaus Geißler, Uwe Platzbecker, Jan Novák, Valeria Santini, Nicola Stefano Fracchiolla, Jürgen Krauter, Yuri Sano, Montserrat Arnán
article en
17 citations

Abstract

This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m<sup>2</sup> 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.

British Journal of HaematologyVol. 205(5)
Sigmund Freud Privatuniversität Wien (AT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Debrecen (HU), University of Freiburg (DE), Charles University (CZ), Masaryk University (CZ), Universitätsklinikum Gießen und Marburg (DE), Queen Elizabeth II Health Sciences Centre (CA), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Hospital General Universitario Gregorio Marañón (ES), University Hospital Ostrava (CZ), University Hospital Brno (CZ), Institut Català d'Oncologia (ES), Klinikum Braunschweig (DE), Azienda Ospedaliero Universitaria Maggiore della Carita (IT), Taiho Oncology (United States) (US), University Hospital Leipzig (DE), Duran i Reynals Hospital (ES), University Hospital Kralovske Vinohrady (CZ), Instituto de Investigación Sanitaria del Principado de Asturias (ES), University of Florence (IT)
Astex Pharmaceuticals
Good health and well-being
Openalex Percentile: Top 2%
Acute Myeloid Leukemia Research
7.72
DOIOpen Access PDFOpenAlex
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