{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:36:24Z","timestamp":1777876584119,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>This phase 1 study aims to evaluate the tolerability and the recommended phase 2 dose of selinexor in Asian patients with advanced or metastatic malignancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Design:<\/jats:title>\n                    <jats:p>\n                      A total of 105 patients with advanced malignancies were enrolled from two sites in Singapore (National University Hospital and the National Cancer Centre, Singapore) from 24 February 2014 to 14 January 2019. We investigated four dosing schedules of selinexor in a 3\u2009+\u20093 dose escalation design with an additional Phase 1b expansion cohort. Adverse events were graded with the NCI Common Terminology Criteria for Adverse Events v 4.03. Pharmacodynamic assessments included nuclear cytoplasmic localization of p27, XPO1 cargo proteins pre and post selinexor dosing and pharmacokinetic assessments were conducted at doses between 40 and 60\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In our Asian patient cohort, dosing at 40\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      given 2 out of 3\u2009weeks, was the most tolerable for our patients. At this dose level, grade 3 adverse events included fatigue (8%), hyponatremia (23%), vomiting (5%), thrombocytopenia (5%), and anaemia (2%). Selinexor had a rapid oral absorption with median T\n                      <jats:sub>max<\/jats:sub>\n                      of 2\u2009h and no PK accumulation after multiple doses of tested regimens. Complete responses were seen in two lymphoma patients. Partial responses were noted in three diffuse large B cell lymphomas, one Hodgkin\u2019s lymphoma and thymic carcinoma patient, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Selinexor is tolerated by Asian patients at 40\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      twice a week given 2 out of 3\u2009weeks. A 1-week drug holiday was needed as our patients could not tolerate the current approved continuous dosing regimens because of persistent grade 3 fatigue, anorexia and hyponatremia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359221087555","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T01:13:11Z","timestamp":1649725991000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies"],"prefix":"10.1177","volume":"14","author":[{"given":"Jingshan","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Heong","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tan Tock Seng Hospital, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Peng Yong","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross","family":"Soo","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Ean Chee","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, 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Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Yan Pang","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscillia","family":"Koe","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santhiay","family":"Nathan Jeraj","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyu","family":"Pyar Soe","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology, National University Cancer Institute Singapore, 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