The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: a phase I, open-label, single dose-escalation study. Issue 4 (April 2013)

• Record Type: Journal Article
• Authors: Vose, Julie M.; Friedberg, Jonathan W.; Waller, Edmund K.; Cheson, Bruce D.; Juvvigunta, Vasthala; Fritsch, Holger; Petit, Claude; Munzert, Gerd; Younes, Anas
• Is Part Of: Leukemia & lymphoma. Volume 54:Issue 4(2013:Apr.)
• Page Start: 708
• Page End: 713
• Publication Date: 2013-04
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2012.729833
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>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 (<italic>n</italic> = 17) and transplant-naive (<italic>n</italic> = 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.</p> </abstract>