-
Something wrong with this record ?
Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study
K. Geissler, Z. Koristek, TB. Del Castillo, J. Novák, G. Rodríguez-Macías, SK. Metzelder, A. Illes, J. Mayer, M. Arnan, MM. Keating, J. Krauter, M. Lunghi, NS. Fracchiolla, U. Platzbecker, V. Santini, Y. Sano, A. Oganesian, H. Keer, M. Lübbert
Language English Country England, Great Britain
Document type Journal Article, Randomized Controlled Trial, Multicenter Study, Comparative Study
Grant support
Astex Pharmaceuticals, Inc., now part of Taiho Oncology, Inc.
PubMed
39313917
DOI
10.1111/bjh.19741
Knihovny.cz E-resources
- MeSH
- Leukemia, Myeloid, Acute * drug therapy mortality MeSH
- Administration, Oral MeSH
- Decitabine * administration & dosage pharmacokinetics adverse effects therapeutic use MeSH
- Adult MeSH
- Administration, Intravenous MeSH
- Cross-Over Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use pharmacokinetics adverse effects administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Uridine * analogs & derivatives administration & dosage pharmacokinetics adverse effects therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m2 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.
Azienda Ospedaliero Universitaria Maggiore Della Carità Novara Novara Italy
Department of Haematooncology University Hospital Ostrava Ostrava Czech Republic
Fakultní Nemocnice Brno and Masaryk University Brno Czech Republic
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico SC Ematologia Milan Italy
Hospital General Universitario Gregorio Marañón Madrid Spain
Institut Català d'Oncologia Hospital Duran i Reynals Barcelona Spain
MDS Unit Hematology AOUC DMSC Università degli Studi di Firenze Firenze Italy
Philipps University Marburg and University Hospital Gießen and Marburg Marburg Germany
Queen Elizabeth 2 Health Sciences Centre Halifax Nova Scotia Canada
Sigmund Freud PrivatUniversität Wien Austria
Städtisches Klinikum Braunschweig Klinik für Hämatologie und Onkologie Braunschweig Germany
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc25003634
- 003
- CZ-PrNML
- 005
- 20250206104454.0
- 007
- ta
- 008
- 250121s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1111/bjh.19741 $2 doi
- 035 __
- $a (PubMed)39313917
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Geissler, Klaus $u Sigmund Freud PrivatUniversität, Wien, Austria $1 https://orcid.org/0000000319217034
- 245 10
- $a Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study / $c K. Geissler, Z. Koristek, TB. Del Castillo, J. Novák, G. Rodríguez-Macías, SK. Metzelder, A. Illes, J. Mayer, M. Arnan, MM. Keating, J. Krauter, M. Lunghi, NS. Fracchiolla, U. Platzbecker, V. Santini, Y. Sano, A. Oganesian, H. Keer, M. Lübbert
- 520 9_
- $a This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m2 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.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a decitabin $x aplikace a dávkování $x farmakokinetika $x škodlivé účinky $x terapeutické užití $7 D000077209
- 650 12
- $a akutní myeloidní leukemie $x farmakoterapie $x mortalita $7 D015470
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a lidé středního věku $7 D008875
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a aplikace orální $7 D000284
- 650 _2
- $a senioři $7 D000368
- 650 12
- $a uridin $x analogy a deriváty $x aplikace a dávkování $x farmakokinetika $x škodlivé účinky $x terapeutické užití $7 D014529
- 650 _2
- $a dospělí $7 D000328
- 650 12
- $a protokoly protinádorové kombinované chemoterapie $x terapeutické užití $x farmakokinetika $x škodlivé účinky $x aplikace a dávkování $7 D000971
- 650 _2
- $a klinické křížové studie $7 D018592
- 650 _2
- $a senioři nad 80 let $7 D000369
- 650 _2
- $a intravenózní podání $7 D061605
- 650 _2
- $a výsledek terapie $7 D016896
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a randomizované kontrolované studie $7 D016449
- 655 _2
- $a multicentrická studie $7 D016448
- 655 _2
- $a srovnávací studie $7 D003160
- 700 1_
- $a Koristek, Zdenek $u Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic
- 700 1_
- $a Del Castillo, Teresa Bernal $u Hospital Universitario Central de Asturias, Instituo de Investigación Sanitaria del Principado de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain $1 https://orcid.org/000000022338513X
- 700 1_
- $a Novák, Jan $u Department of Haematology, Third Faculty of Medicine, Charles University and Faculty Hospital University, Hospital Královské Vinohrady, Prague, Czech Republic
- 700 1_
- $a Rodríguez-Macías, Gabriela $u Hospital General Universitario Gregorio Marañón, Madrid, Spain
- 700 1_
- $a Metzelder, Stephan K $u Philipps University Marburg and University Hospital Gießen and Marburg, Marburg, Germany
- 700 1_
- $a Illes, Arpad $u Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary
- 700 1_
- $a Mayer, Jiří $u Fakultní Nemocnice Brno and Masaryk University, Brno, Czech Republic
- 700 1_
- $a Arnan, Montserrat $u Institut Català d'Oncologia-Hospital Duran i Reynals, Barcelona, Spain
- 700 1_
- $a Keating, Mary-Margaret $u Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
- 700 1_
- $a Krauter, Jürgen $u Städtisches Klinikum Braunschweig, Klinik für Hämatologie und Onkologie, Braunschweig, Germany
- 700 1_
- $a Lunghi, Monia $u Azienda Ospedaliero-Universitaria Maggiore Della Carità Novara, Novara, Italy
- 700 1_
- $a Fracchiolla, Nicola Stefano $u Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, SC Ematologia, Milan, Italy
- 700 1_
- $a Platzbecker, Uwe $u Universitätsklinikum Leipzig, Leipzig, Germany
- 700 1_
- $a Santini, Valeria $u MDS Unit, Hematology, AOUC, DMSC, Università degli Studi di Firenze, Firenze, Italy $1 https://orcid.org/0000000254392172
- 700 1_
- $a Sano, Yuri $u Taiho Oncology, Inc., Pleasanton, California, USA
- 700 1_
- $a Oganesian, Aram $u Taiho Oncology, Inc., Pleasanton, California, USA
- 700 1_
- $a Keer, Harold $u Taiho Oncology, Inc., Pleasanton, California, USA $1 https://orcid.org/0000000307534921
- 700 1_
- $a Lübbert, Michael $u Department of Haematology, Oncology, and Stem Cell Transplantation, University of Freiburg Medical Center, University of Freiburg Faculty of Medicine, Freiburg, Germany $1 https://orcid.org/0000000311861650
- 773 0_
- $w MED00009374 $t British journal of haematology $x 1365-2141 $g Roč. 205, č. 5 (2024), s. 1734-1745
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/39313917 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20250121 $b ABA008
- 991 __
- $a 20250206104449 $b ABA008
- 999 __
- $a ok $b bmc $g 2263406 $s 1239641
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 205 $c 5 $d 1734-1745 $e 20240923 $i 1365-2141 $m British journal of haematology $n Br J Haematol $x MED00009374
- GRA __
- $p Astex Pharmaceuticals, Inc., now part of Taiho Oncology, Inc.
- LZP __
- $a Pubmed-20250121
