PURPOSE: @entity13449 is the first cyclin-dependent kinase (cdk) inhibitor to enter clinical trials. Serum levels of @entity13449 obtained during phase I studies were sufficient to inhibit in vitro @entity5 cell growth. Because responses were observed in @entity703 @entity1 in the phase I trials, we performed a phase II trial of @entity13449 in this @entity1 population. @entity1 AND METHODS: Thirty-five minimally pretreated @entity1 were accrued using a standard two-step mechanism. @entity13449 (50 mg/m(2)/d) was administered by continuous infusion for 72 hours every 2 weeks, and response was evaluated every 8 weeks. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, at completion of drug infusion, and on day 7 of the first therapy cycle, and cell cycle parameters after phytohemagglutinin and @entity1199 stimulation were assessed. RESULTS: There were two objective responses (response rate = 6%, 95% confidence interval, 1% to 20%). The most common @entity137 were @entity1395 , occurring in 83% of @entity1 (grade 3 or 4 in 9%), and @entity294 , occurring in 77% of @entity1 (grade 3 or 4 in 20%). Also, nine @entity1 (26%) experienced grade 3 or 4 vascular thrombotic events, including one @entity583 , two transient neurologic @entity63 attacks, four @entity1150 , and two @entity1151 . Cell cycle studies did not reveal any effect of @entity13449 on stimulated PBMCs. CONCLUSION: @entity13449 , at the dose and schedule administered in this trial, is ineffective in metastatic @entity703 . In addition to the @entity294 observed in phase I studies, we also observed a higher incidence of @entity1395 and serious vascular thrombotic events than expected.

@entity13449 , a novel cyclin-dependent kinase inhibitor, in metastatic XXXX : a University of Chicago Phase II Consortium study.

@entity13449 :: ('MESH:C077990', 'Chemical') :: ['Flavopiridol', 'flavopiridol'] @entity1 :: ('9606', 'Species') :: ['patients', 'patient', 'PATIENTS'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity1395 :: ('MESH:D001247', 'Disease') :: ['asthenia'] @entity1151 :: ('MESH:D011655', 'Disease') :: ['pulmonary emboli'] @entity1150 :: ('MESH:D020246', 'Disease') :: ['deep venous thrombosis'] @entity1199 :: ('3558', 'Gene') :: ['interleukin-2'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction'] @entity703 :: ('MESH:D007680', 'Disease') :: ['renal cancer', 'kidney cancer']
@entity703 :: (MESH:D007680,Disease) :: ['renal cancer']
