title: Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity.
abstract: BACKGROUND
  This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and activity of volasertib, a selective Polo-like kinase 1 inhibitor that induces mitotic arrest and apoptosis, combined with cisplatin or carboplatin in patients with advanced/metastatic solid tumors (NCT00969761; 1230.6).
  
  
  METHODS
  Sequential patient cohorts (3 + 3 dose-escalation design) received a single infusion of volasertib (100-350 mg) with cisplatin (60-100 mg/m(2)) or carboplatin (area under the concentration versus time curve [AUC]4-AUC6) on day 1 every 3 weeks for up to six cycles. Sixty-one patients received volasertib/cisplatin (n = 30) or volasertib/carboplatin (n = 31) for a median of 3.5 (range, 1-6) and 2.0 (range, 1-6) treatment cycles, respectively.
  
  
  RESULTS
  The most common cycle 1 dose-limiting toxicities (DLTs) were thrombocytopenia, neutropenia and fatigue. MTDs (based on cycle 1 DLTs) were determined to be volasertib 300 mg plus cisplatin 100 mg/m(2) and volasertib 300 mg plus carboplatin AUC6. Co-administration did not affect the pharmacokinetics of each drug. Partial responses were observed in two patients in each arm. Stable disease was achieved in 11 and six patients treated with volasertib/cisplatin and volasertib/carboplatin, respectively.
  
  
  CONCLUSIONS
  Volasertib plus cisplatin or carboplatin at full single-agent doses was generally manageable and demonstrated activity in heavily pretreated patients with advanced solid tumors.
authors: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121, B-1000, Brussels, Belgium, ahmad.awada@bordet.be.
authors: Ahmad
authors: A
authors: Awada
authors: Herlinde
authors: H
authors: Dumez
authors: Philippe G
authors: PG
authors: Aftimos
authors: Jo
authors: J
authors: Costermans
authors: Sylvie
authors: S
authors: Bartholomeus
authors: Kathleen
authors: K
authors: Forceville
authors: Thierry
authors: T
authors: Berghmans
authors: Marie-Anne
authors: MA
authors: Meeus
authors: Jessica
authors: J
authors: Cescutti
authors: Gerd
authors: G
authors: Munzert
authors: Korinna
authors: K
authors: Pilz
authors: Dan
authors: D
authors: Liu
authors: Patrick
authors: P
authors: Schöffski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010984:Platinum / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011621:Pteridines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D055815:Young Adult; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D018797:Cell Cycle Proteins; D002945:Cisplatin; D010984:Platinum; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D000097869:Polo-Like Kinase 1; C541363:BI 6727