TY - JOUR
T1 - The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma
T2 - A phase I, open-label, single dose-escalation study
AU - Vose, Julie M.
AU - Friedberg, Jonathan W.
AU - Waller, Edmund K.
AU - Cheson, Bruce D.
AU - Juvvigunta, Vasthala
AU - Fritsch, Holger
AU - Petit, Claude
AU - Munzert, Gerd
AU - Younes, Anas
N1 - Funding Information:
The study was funded by Boehringer Ingelheim. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Victoria A. Robb, of GeoMed, during the preparation of this manuscript.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
KW - BI 2536
KW - Non-Hodgkin lymphoma
KW - Single dose-escalation study
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U2 - 10.3109/10428194.2012.729833
DO - 10.3109/10428194.2012.729833
M3 - Article
C2 - 22978685
AN - SCOPUS:84877112319
SN - 1042-8194
VL - 54
SP - 708
EP - 713
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 4
ER -