{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:58:28Z","timestamp":1793303908401,"version":"4.5.0"},"reference-count":25,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This phase 2 study was designed to compare systemic decitabine exposure, demethylation activity, and safety in the first 2 cycles with cedazuridine 100 mg\/decitabine 35 mg vs standard decitabine 20 mg\/m2 IV. Adults with International Prognostic Scoring System intermediate-1\/2- or high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) were randomized 1:1 to receive oral cedazuridine\/decitabine or IV decitabine in cycle 1, followed by crossover to the other treatment in cycle 2. All patients received oral cedazuridine\/decitabine in subsequent cycles. Cedazuridine and decitabine were given initially as separate capsules in a dose-confirmation stage and then as a single fixed-dose combination (FDC) tablet. Primary end points: mean decitabine systemic exposure (geometric least-squares mean [LSM]) of oral\/IV 5-day area under curve from time 0 to last measurable concentration (AUClast), percentage long interspersed nuclear element 1 (LINE-1) DNA demethylation for oral cedazuridine\/decitabine vs IV decitabine, and clinical response. Eighty patients were randomized and treated. Oral\/IV ratios of geometric LSM 5-day AUClast (80% confidence interval) were 93.5% (82.1-106.5) and 97.6% (80.5-118.3) for the dose-confirmation and FDC stages, respectively. Differences in mean %LINE-1 demethylation between oral and IV were \u22641%. Clinical responses were observed in 48 patients (60%), including 17 (21%) with complete response. The most common grade \u22653 adverse events regardless of causality were neutropenia (46%), thrombocytopenia (38%), and febrile neutropenia (29%). Oral cedazuridine\/decitabine (100\/35 mg) produced similar systemic decitabine exposure, DNA demethylation, and safety vs decitabine 20 mg\/m2 IV in the first 2 cycles, with similar efficacy. This study is registered at www.clinicaltrials.gov as #NCT02103478.<\/jats:p>","DOI":"10.1182\/blood.2019004143","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T19:28:19Z","timestamp":1586806099000},"page":"674-683","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":207,"title":["Oral cedazuridine\/decitabine for MDS and CMML: a phase 2 pharmacokinetic\/pharmacodynamic randomized crossover study"],"prefix":"10.1182","volume":"136","author":[{"given":"Guillermo","family":"Garcia-Manero","sequence":"first","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, 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