Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors

摘要: Purpose This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and clinical effects of volasertib, a selective Polo-like kinase inhibitor that induces mitotic arrest apoptosis, in Japanese patients with advanced solid tumors (NCT01348347; 1230.15). Methods In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 design) received volasertib (200–350 mg) as single by intravenous infusion over 2 h on day 1 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was MTD an tumor; secondary endpoints included benefit. Results Fifteen tumor were treated. Dose-limiting toxicities grade 4 neutropenia for ≥7 thrombocytopenia both experienced 2/6 350 mg cohort. 300 mg. most common (≥3 patients) drug-related non-hematologic adverse events fatigue, decreased appetite, nausea. Exposure to its metabolite increased increasing doses. A partial response gastric cancer stable eleven observed. Conclusions Volasertib had manageable safety profile up determined is comparable those previously obtained Caucasian patients. These data support enrollment global trials without modification.