Klaus Geissler, Zdenek Koristek, Teresa Bernal Del Castillo, Jan Novák, Gabriela Rodríguez-Macías, Stephan K Metzelder, Arpad Illes, Jiří Mayer, Montserrat Arnan, Mary-Margaret Keating, Jürgen Krauter, Monia Lunghi, Nicola Stefano Fracchiolla, Uwe Platzbecker, Valeria Santini, Yuri Sano, Aram Oganesian, Harold Keer, Michael Lübbert
{"title":"急性髓性白血病口服地西他滨/西达嘧啶与静脉注射地西他滨的比较:一项随机、交叉、注册、药代动力学研究。","authors":"Klaus Geissler, Zdenek Koristek, Teresa Bernal Del Castillo, Jan Novák, Gabriela Rodríguez-Macías, Stephan K Metzelder, Arpad Illes, Jiří Mayer, Montserrat Arnan, Mary-Margaret Keating, Jürgen Krauter, Monia Lunghi, Nicola Stefano Fracchiolla, Uwe Platzbecker, Valeria Santini, Yuri Sano, Aram Oganesian, Harold Keer, Michael Lübbert","doi":"10.1111/bjh.19741","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study.\",\"authors\":\"Klaus Geissler, Zdenek Koristek, Teresa Bernal Del Castillo, Jan Novák, Gabriela Rodríguez-Macías, Stephan K Metzelder, Arpad Illes, Jiří Mayer, Montserrat Arnan, Mary-Margaret Keating, Jürgen Krauter, Monia Lunghi, Nicola Stefano Fracchiolla, Uwe Platzbecker, Valeria Santini, Yuri Sano, Aram Oganesian, Harold Keer, Michael Lübbert\",\"doi\":\"10.1111/bjh.19741\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":135,\"journal\":{\"name\":\"British Journal of Haematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Haematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/bjh.19741\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Haematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/bjh.19741","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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/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.
期刊介绍:
The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.