BACKGROUND: Systemic treatment of @entity320 is largely ineffective and alternative approaches are needed. @entity2213 mesylate is an oral @entity669 kinase inhibitor that targets @entity1861 , @entity2467 , platelet-derived growth factor receptor ( @entity675 , and @entity3820 , leading to remarkable clinical responses in several @entity5 . Signal transduction via @entity2467 , @entity675 , and @entity3820 has been demonstrated in @entity320 . METHODS: The primary objective of this Phase II study was to determine the response rate, response duration, and the frequency of 6-month progression-free survival in @entity1 who could receive up to 2 prior therapeutic regimens. Initially, @entity1 received @entity2213 at at dose of 400 mg twice orally each day. Based on Simon's optimal design, the study allowed entry of 21 @entity1 ; if there were > or = 2 objective responses, accrual would then continue to a total of 41 @entity1 . RESULTS: Twenty-six @entity1 were enrolled. @entity1 experienced 29 episodes of Grade 3 and 2 episodes of Grade 4 @entity137 (according to National @entity5 Institute common @entity137 criteria). No objective clinical responses were noted among the 25 evaluable @entity1 . The median time to progression was 54 days and the median overall survival was 200 days. No @entity1 was free of disease progression at 6 months. @entity982 -embedded @entity5 specimens from 15 @entity1 were tested for expression of @entity2213 responsive kinases by immunohistochemistry. Three @entity5 had moderate and 5 @entity5 had weak staining for @entity2467 . Five @entity5 samples had weak staining for @entity675 and -beta. CONCLUSIONS: @entity2213 is an inactive single agent in @entity320 in a population of predominantely pretreated @entity1 . The levels of @entity2467 and/or @entity675 , -beta expression in the current study were lower than previously reported. Alternative treatment strategies remain a priority for @entity1 with advanced @entity320 .

Multicenter Phase II trial of high-dose @entity2213 in XXXX : significant @entity137 with no clinical efficacy.

@entity675 :: ('5156', 'Gene') :: ['PDGFR-alpha', 'PDGFR)-alpha'] @entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient'] @entity1861 :: ('25', 'Gene') :: ['bcr-Abl'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Cancer', 'cancers', 'tumors'] @entity3820 :: ('5159', 'Gene') :: ['PDGFR-beta'] @entity982 :: ('MESH:D010232', 'Chemical') :: ['Paraffin'] @entity2467 :: ('3815', 'Gene') :: ['c-kit'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity2213 :: ('MESH:C097613', 'Chemical') :: ['imatinib', 'Imatinib'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'metastatic melanoma', 'malignant melanoma']
@entity320 :: (MESH:D008545,Disease) :: ['metastatic melanoma']
