CHIA-CHI LINSu W.-C.Yen C.-J.CHIH-HUNG HSUSu W.-P.KUN-HUEI YEHYEN-SHEN LUANN-LII CHENGHuang D.C.-L.Fritsch H.Voss F.Taube T.CHIH-HSIN YANG2020-04-282020-04-2820140007-0920https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900540918&doi=10.1038%2fbjc.2014.195&partnerID=40&md5=4d612692a3e73210725c2389d3fee7ebhttps://scholars.lib.ntu.edu.tw/handle/123456789/487292Background:Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours.Methods:Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course.Results:Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ?135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile.Conclusions:These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients. ? 2014 Cancer Research UK.[SDGs]SDG3alanine aminotransferase; polo like kinase inhibitor; volasertib; abdominal distension; abdominal pain; adult; advanced cancer; aged; alanine aminotransferase blood level; anemia; article; Asian; decreased appetite; dizziness; drug clearance; drug distribution; drug dose increase; drug effect; drug efficacy; drug half life; drug safety; drug tolerability; dyspnea; fatigue; febrile neutropenia; female; gastrointestinal hemorrhage; human; hypokalemia; ileus; infection; leukopenia; major clinical study; male; maximum tolerated dose; melanoma; neutropenia; pain; phase 1 clinical trial; priority journal; solid tumor; thrombocytopenia; tinnitus; ureter cancer; Adult; Aged; Antineoplastic Agents; Cell Cycle Proteins; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Half-Life; Hematologic Diseases; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Proteins; Neoplasms; Protein Kinase Inhibitors; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Pteridines; Salvage Therapy; Taiwan; Treatment Outcomejournal article10.1038/bjc.2014.195247558822-s2.0-84900540918