کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2754544 1149787 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Phase II, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of P276-00, a Cyclin-Dependent Kinase Inhibitor, in Patients With Relapsed or Refractory Mantle Cell Lymphoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
پیش نمایش صفحه اول مقاله
A Phase II, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of P276-00, a Cyclin-Dependent Kinase Inhibitor, in Patients With Relapsed or Refractory Mantle Cell Lymphoma
چکیده انگلیسی

IntroductionOverexpression of cyclin D1 is a hallmark feature of mantle cell lymphoma (MCL). Many of the oncogenic effects of cyclin D1 are mediated through cyclin-dependent kinases (CDKs). P276-00 is a potent small molecule inhibitor of CDK4-D1, CDK1-B, and CDK9-T, with promising activity in preclinical models. In phase I studies of P276-00 in patients with refractory solid neoplasms, it was well-tolerated with a mild trend toward single-agent efficacy.Patients and MethodsA phase II study of P276-00 was conducted in patients with relapsed or refractory MCL at the recommended dose of 185 mg/m2/day from days 1 to 5 of a 21-day cycle. Thirteen patients were enrolled in the present study.ResultsOf the 13 patients, 11 experienced disease progression, 1 patient was withdrawn because of an adverse event (AE), and 1 patient died. Also, 11 patients (84.6%) experienced a treatment-emergent AE deemed related to P276-00. Of the 13 patients, 9 (69.2%) received ≥ 2 cycles of treatment, which was the predefined threshold to be evaluable for efficacy. Treatment was discontinued early in 2 patients because of AEs (1 of which was attributed to P276-00 administration) and in 2 patients because of disease progression. Finally, 2 patients experienced stable disease for an estimated median duration of 60.5 days (range, 58-63 days). The estimated median time to progression for the predefined efficacy population was 43 days (range, 38-58 days).ConclusionGiven the results observed in the present study, if evaluation of CDK inhibition in MCL continues, it should be considered earlier in the disease course or as a part of combination strategies for relapsed or refractory disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Lymphoma Myeloma and Leukemia - Volume 15, Issue 7, July 2015, Pages 392–397
نویسندگان
, , , , , , ,