{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:30:02Z","timestamp":1775064602306,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B\u2010cell non\u2010Hodgkin\u2010type lymphoma (B\u2010NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tazemetostat was given orally at a single dose of 800\u00a0mg on the first day and 800\u00a0mg twice daily (BID: total 1600\u00a0mg\/d) on following days in a 28\u2010day\/cycle manner. Tazemetostat dose\u2010limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot <jats:italic>EZH2<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B\u2010cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59\u201085)\u00a0years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment\u2010related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment\u2010related serious AEs were observed. The objective response rate was 57% (4\/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An <jats:italic>EZH2<\/jats:italic> mutation was detected in one patient with FL responding to treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tazemetostat at 800\u00a0mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B\u2010NHL.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cas.14822","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T19:53:31Z","timestamp":1611604411000},"page":"1123-1131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B\u2010cell lymphoma"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4679-0656","authenticated-orcid":false,"given":"Wataru","family":"Munakata","sequence":"first","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari","family":"Shirasugi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensei","family":"Tobinai","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Onizuka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-8088","authenticated-orcid":false,"given":"Shinichi","family":"Makita","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-6920","authenticated-orcid":false,"given":"Dai","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetsugu","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Izutsu","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Eisai Co., Ltd. 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