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.
- MeSH
- akutní myeloidní leukemie * farmakoterapie mortalita MeSH
- aplikace orální MeSH
- decitabin * aplikace a dávkování farmakokinetika škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- intravenózní podání MeSH
- klinické křížové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití farmakokinetika škodlivé účinky aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- uridin * analogy a deriváty aplikace a dávkování farmakokinetika škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
