{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T07:34:51Z","timestamp":1771054491715,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low\u2010intensity therapy, to elderly patients with newly diagnosed AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This randomized, open\u2010label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged \u226570 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1\u2010hour intravenous infusions of decitabine 20 mg\/m<jats:sup>2<\/jats:sup> once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1\u2010hour infusions of decitabine 20 mg\/m<jats:sup>2<\/jats:sup> once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (&lt;10 \u00d7 10<jats:sup>9<\/jats:sup>\/L and \u226510 \u00d7 10<jats:sup>9<\/jats:sup>\/L), and bone marrow blast percentage (\u226550% vs &lt;50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1\u2010year survival. The trial is registered at ClinicalTrials.gov (NCT01303796).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (<jats:italic>P<\/jats:italic> = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (<jats:italic>P<\/jats:italic> = .1468). In patients with white blood cell counts &lt;10 \u00d7 10<jats:sup>9<\/jats:sup>\/L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; <jats:italic>P<\/jats:italic> = .145), as was the CR rate (21.5% vs 8.6%; <jats:italic>P<\/jats:italic> = .0017).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts &lt;10 \u00d7 10<jats:sup>9<\/jats:sup>\/L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33828","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T10:43:16Z","timestamp":1629715396000},"page":"4421-4431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS)"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop M.","family":"Kantarjian","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2730-8593","authenticated-orcid":false,"given":"Kebede H.","family":"Begna","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica K.","family":"Altman","sequence":"additional","affiliation":[{"name":"Department of Medicine Northwestern University Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-4082","authenticated-orcid":false,"given":"Stuart L.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2009-6524","authenticated-orcid":false,"given":"Mikkael A.","family":"Sekeres","sequence":"additional","affiliation":[{"name":"Hematologic Oncology and Blood Disorders Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6861-2041","authenticated-orcid":false,"given":"Stephen A.","family":"Strickland","sequence":"additional","affiliation":[{"name":"Vanderbilt\u2010Ingram Cancer Center Nashville Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1636-1962","authenticated-orcid":false,"given":"Martha L.","family":"Arellano","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology Emory University School of Medicine Atlanta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9209-2405","authenticated-orcid":false,"given":"David F.","family":"Claxton","sequence":"additional","affiliation":[{"name":"Penn State Milton S. 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