{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:32:58Z","timestamp":1790695978981,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,10,21]],"date-time":"2015-10-21T00:00:00Z","timestamp":1445385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Nippon Boehringer Ingelheim Co., Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>This phase I trial conducted in Japanese patients with acute myeloid leukemia evaluated the safety, maximum tolerated dose and pharmacokinetics of volasertib (BI 6727), a selective Polo\u2010like kinase inhibitor. The primary endpoints were the maximum tolerated dose of volasertib and the incidence of dose\u2010limiting toxicities. Secondary endpoints were best response and remission duration. Other endpoints included safety and pharmacokinetics. Patients who were ineligible for standard induction therapy or with relapsed or refractory disease received volasertib monotherapy as a 2\u2010h infusion on days 1 and 15 of a 28\u2010day cycle, with dose escalation following a 3 + 3 design. A total of 19 patients were treated with three volasertib doses: 350, 400 and 450 mg. One patient receiving volasertib 450 mg reported a dose\u2010limiting toxicity of grade 4 abnormal liver function test and 450 mg was determined as the maximum tolerated dose. The most frequently reported adverse events were febrile neutropenia (78.9%), decreased appetite (42.1%), nausea and rash (36.8% each), and sepsis, fatigue, hypokalemia, stomatitis and epistaxis (26.3% each). Best responses were complete remission (<jats:italic>n =<\/jats:italic> 3), complete remission with incomplete blood count recovery (<jats:italic>n<\/jats:italic> = 3) and partial remission (<jats:italic>n<\/jats:italic> = 1). The median remission duration of the six patients with complete remission or complete remission with incomplete blood count recovery was 85 days (range 56\u2013358). Volasertib exhibited multi\u2010compartmental pharmacokinetic behavior with a fast distribution after the end of infusion followed by slower elimination phases. Volasertib monotherapy was clinically manageable with acceptable adverse events and anti\u2010leukemic activity.<\/jats:p>","DOI":"10.1111\/cas.12814","type":"journal-article","created":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T12:27:31Z","timestamp":1441888051000},"page":"1590-1595","source":"Crossref","is-referenced-by-count":41,"title":["Phase I trial of volasertib, a Polo\u2010like kinase inhibitor, in Japanese patients with acute myeloid leukemia"],"prefix":"10.1111","volume":"106","author":[{"given":"Yukio","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Hematology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology University of Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kiyoi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Sakura","sequence":"additional","affiliation":[{"name":"Leukemia Research Center Saiseikai Maebashi Hospital Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagasaki University Hospital Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Tokai University School of Medicine Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Watabe","sequence":"additional","affiliation":[{"name":"Clinical Trial Management Department Nippon Boehringer Ingelheim Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Harada","sequence":"additional","affiliation":[{"name":"Clinical PK\/PD Department Nippon Boehringer Ingelheim Co., Ltd Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tillmann","family":"Taube","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG Biberach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagasaki University Hospital Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Naoe","sequence":"additional","affiliation":[{"name":"National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,21]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"National Comprehensive Cancer Network (NCCN).Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 1.2015. 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