title: The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: a phase I, open-label, single dose-escalation study.
abstract: Polo-like kinase 1 (Plk1) is expressed during mitosis and overexpressed in multiple cancers, including non-Hodgkin lymphoma (NHL). This phase I study determined the maximum tolerated dose (MTD) of BI 2536, a Plk1 inhibitor, as a 1 h infusion once every 3 weeks in post-transplant relapsed (n = 17) and transplant-naive (n = 24) patients with relapsed/refractory NHL. Median treatment cycles were 2 and 1.5, respectively. MTD was 175 mg for both populations; dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia. Most treatment-related adverse events were grade 1/2; drug-related grade 3/4 events included thrombocytopenia and neutropenia. Four patients achieved responses (three complete and one partial at doses ≥ 150 mg, all post-transplant relapsed patients) for an overall response rate of 9.8%. BI 2536 exhibited multi-compartmental pharmacokinetics with a high volume of distribution. The activity and safety of BI 2536 in this pretreated patient population support Plk inhibitors as a therapeutic strategy in oncology.
authors.affiliation: University of Nebraska Medical Center, Omaha, NE 68198-7680, USA. jmvose@unmc.edu
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Vasthala
authors.initials: V
authors.lastname: Juvvigunta
authors.forename: Holger
authors.initials: H
authors.lastname: Fritsch
authors.forename: Claude
authors.initials: C
authors.lastname: Petit
authors.forename: Gerd
authors.initials: G
authors.lastname: Munzert
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011621:Pteridines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D000097869:Polo-Like Kinase 1; C518477:BI 2536