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

J 2024

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

GEISSLER, Klaus, Zdenek KORISTEK, del Castillo Teresa BERNAL, Jan NOVAK, Gabriela RODRIGUEZ-MACIAS et. al.

Basic information

Original name

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

Authors

Edition

British journal of haematology, Hoboken, Wiley-Blackwell, 2024, 0007-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1111/bjh.19741

UT WoS

001318836700001

Keywords in English

acute myeloid leukaemia; decitabine/cedazuridine; DNA methyltransferase inhibitors; hypomethylating agents; somatic mutations

Abstract

V originále

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.

Citovat

GEISSLER, Klaus, Zdenek KORISTEK, del Castillo Teresa BERNAL, Jan NOVAK, Gabriela RODRIGUEZ-MACIAS, Stephan K METZELDER, Arpad ILLES, Jiří MAYER, Montserrat ARNAN, Mary-Margaret KEATING, Juergen KRAUTER, Monia LUNGHI, Nicola Stefano FRACCHIOLLA, Uwe PLATZBECKER, Valeria SANTINI, Yuri SANO, Aram OGANESIAN, Harold KEER and Michael LUEBBERT. Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study. British journal of haematology. Hoboken: Wiley-Blackwell, 2024, p. 1-12. ISSN 0007-1048. Available from: https://dx.doi.org/10.1111/bjh.19741.

@article{2439078,
   author = {Geissler, Klaus and Koristek, Zdenek and Bernal, del Castillo Teresa and Novak, Jan and RodriguezandMacias, Gabriela and Metzelder, Stephan K and Illes, Arpad and Mayer, Jiří and Arnan, Montserrat and Keating, MaryandMargaret and Krauter, Juergen and Lunghi, Monia and Fracchiolla, Nicola Stefano and Platzbecker, Uwe and Santini, Valeria and Sano, Yuri and Oganesian, Aram and Keer, Harold and Luebbert, Michael},
   article_location = {Hoboken},
   doi = {http://dx.doi.org/10.1111/bjh.19741},
   keywords = {acute myeloid leukaemia; decitabine/cedazuridine; DNA methyltransferase inhibitors; hypomethylating agents; somatic mutations},
   language = {eng},
   issn = {0007-1048},
   journal = {British journal of haematology},
   title = {Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study},
   url = {https://onlinelibrary.wiley.com/doi/10.1111/bjh.19741},
   year = {2024}
}

TY  - JOUR
ID  - 2439078
AU  - 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
PY  - 2024
TI  - Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study
JF  - British journal of haematology
SP  - 1-12
EP  - 1-12
PB  - Wiley-Blackwell
SN  - 00071048
KW  - acute myeloid leukaemia
KW  - decitabine/cedazuridine
KW  - DNA methyltransferase inhibitors
KW  - hypomethylating agents
KW  - somatic mutations
UR  - https://onlinelibrary.wiley.com/doi/10.1111/bjh.19741
N2  - 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.
ER  -

GEISSLER, Klaus, Zdenek KORISTEK, del Castillo Teresa BERNAL, Jan NOVAK, Gabriela RODRIGUEZ-MACIAS, Stephan K METZELDER, Arpad ILLES, Jiří MAYER, Montserrat ARNAN, Mary-Margaret KEATING, Juergen KRAUTER, Monia LUNGHI, Nicola Stefano FRACCHIOLLA, Uwe PLATZBECKER, Valeria SANTINI, Yuri SANO, Aram OGANESIAN, Harold KEER and Michael LUEBBERT. Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study. \textit{British journal of haematology}. Hoboken: Wiley-Blackwell, 2024, p.~1-12. ISSN~0007-1048. Available from: https://dx.doi.org/10.1111/bjh.19741.

Detailed Information on Publication Record