{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:28:12Z","timestamp":1776857292510,"version":"3.51.2"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T00:00:00Z","timestamp":1371772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The multi\u2010kinase inhibitor rigosertib (<jats:styled-content style=\"fixed-case\">ON<\/jats:styled-content> 01910.<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>a) induces mitotic arrest and apoptosis in myeloblasts, while sparing normal cells. The purpose of this study was to determine the pharmacokinetic profile, maximum\u2010tolerated dose (<jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>), safety, and clinical activity of an oral formulation of rigosertib in patients with myelodysplastic syndromes (<jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>). For pharmacokinetic studies, patients received rigosertib in single escalating weekly doses. To determine the <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>, patient cohorts received escalating doses of rigosertib twice daily for 14\u00a0d of a 21\u2010d cycle. Overall, 37 patients were treated. Rigosertib exposure increased with escalating oral doses. Mean absolute oral bioavailability ranged from 13\u00b79% (fed) to 34\u00b78% (fasting) in 12 patients treated at the 560\u00a0mg b.i.d. dose level. Dose\u2010limiting toxicity (grade 3 dysuria and shortness of breath) occurred at the 700\u00a0mg b.i.d. dose. Five patients experienced grade 3 non\u2010haematological toxicity, including symptoms of urothelial inflammation, hypotension and syncope, fatigue and abdominal pain. Encouraging signs of clinical activity included two bone marrow complete remissions in refractory anaemia with excess blasts type 1 patients previously treated with azacitidine. In addition, four patients each achieved transfusion independence and haematological improvements. In conclusion, oral rigosertib is bioavailable and well tolerated, and has clinical activity in patients with <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.12436","type":"journal-article","created":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T16:22:54Z","timestamp":1371831774000},"page":"517-524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Phase <scp>I<\/scp> clinical trial of oral rigosertib in patients with myelodysplastic syndromes"],"prefix":"10.1111","volume":"162","author":[{"given":"Rami S.","family":"Komrokji","sequence":"first","affiliation":[{"name":"Department of Hematological Malignancies H Lee Moffitt Cancer Center and Research Institute Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azra","family":"Raza","sequence":"additional","affiliation":[{"name":"Columbia University Medical Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Lancet","sequence":"additional","affiliation":[{"name":"Department of Hematological Malignancies H Lee Moffitt Cancer Center and Research Institute Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Ren","sequence":"additional","affiliation":[{"name":"Onconova Therapeutics Inc Newtown PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Taft","sequence":"additional","affiliation":[{"name":"Arnold &amp; Marie Schwartz College of Pharmacy and Health Sciences Long Island University Brooklyn NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Maniar","sequence":"additional","affiliation":[{"name":"Onconova Therapeutics Inc Newtown PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Onconova Therapeutics Inc Newtown PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan F.","family":"List","sequence":"additional","affiliation":[{"name":"Department of Hematological Malignancies H Lee Moffitt Cancer Center and Research Institute Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,6,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2113"},{"key":"e_1_2_12_3_1","first-page":"3671","article-title":"Report of an international working group to standardize response criteria for myelodysplastic syndromes","volume":"96","author":"Cheson B.D.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4149"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2004.02.002"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70003-8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.6.2079"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2011.0005"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-420489"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.02.009"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.12.3835"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25247"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.9788"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22376"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-011-0086-x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2007.05.047"},{"key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1182\/blood.V116.21.2913.2913","article-title":"Poor outcome of patients with myelodysplastic syndrome (MDS) after azacitidine treatment failure","volume":"116","author":"Lin K.","year":"2010","journal-title":"Blood"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2012.04.002"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1603"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.502"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.8135"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200570p"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2011.08.022"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1182\/blood.V116.21.3998.3998","article-title":"Overall survival In myelodysplastic syndrome or acute myeloid leukemia patients treated with ON 01910.Na correlates with bone marrow blast response","volume":"116","author":"Silverman L.R.","year":"2010","journal-title":"Blood"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-4296(03)00031-6"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209262"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.12436","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.12436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T21:00:19Z","timestamp":1696280419000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.12436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,21]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/bjh.12436"],"URL":"https:\/\/doi.org\/10.1111\/bjh.12436","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,21]]},"assertion":[{"value":"2013-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}