PURPOSE: The safety and efficacy of oral metronomic low-dose @entity21193 chemotherapy in combination with the @entity3840 ( @entity3840 ) inhibitor @entity13586 as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of @entity5 cells, were assessed in pretreated advanced @entity320 @entity1 . METHODS: Endothelial cells were analyzed for proliferation, apoptosis and @entity137 in response to increasing concentrations of @entity21193 , either in the absence or presence of @entity3840 inhibitor, to determine whether inhibition of @entity3840 enhanced the effect of @entity21193 on cell function. In a clinical pilot study, 12 consecutive @entity1 with pretreated advanced @entity320 , meeting the eligibility criteria were enrolled. @entity1 received combined daily @entity21193 chemotherapy (500 mg) with @entity13586 (25 mg). Metastatic lesions were assessed every 12 weeks. @entity1 with responsive or stable disease were eligible for a further 12-week treatment period. Response criteria according to the WHO handbook for reporting results of @entity5 treatment were applied. Side effects were classified according to the National @entity5 Institute's Common @entity137 Criteria v2.0. RESULTS: At noncytotoxic concentrations, @entity21193 inhibited endothelial cell proliferation in a dose-dependent fashion. Simultaneous inhibition of @entity3840 significantly increased the extent to which @entity21193 suppressed cell proliferation, without inducing @entity137 . In the pilot study in which 12 @entity1 were treated, @entity137 was mild; only hematologic @entity137 of grade II was seen. An objective response was noted in one @entity1 , and four @entity1 showed stabilization of their disease for 24 weeks (one) and 36 weeks (three). The @entity1 who had a partial response subsequently showed stable disease for 48 weeks. The median survival time was 13 months. CONCLUSIONS: As increases in response rates following polychemo- or biochemotherapy have not been shown to correlate with prolongation in overall survival, more durable control of @entity320 represents an attractive therapeutic goal. Thus, regimens scheduled to primarily target endothelial cells may potentially provide a palliative alternative that preserves quality of life in the absence of significant treatment-related @entity137 .

Metronomic oral low-dose XXXX chemotherapy combined with @entity3840 inhibitor in pretreated advanced @entity320 : a pilot study.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient'] @entity13586 :: ('MESH:C116926', 'Chemical') :: ['rofecoxib'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'Toxicity', 'cytotoxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'Cancer'] @entity3840 :: ('5743', 'Gene') :: ['cyclooxygenase-2', 'COX-2'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'metastatic melanoma'] @entity21193 :: ('MESH:C018404', 'Chemical') :: ['treosulfan']
@entity21193 :: (MESH:C018404,Chemical) :: ['treosulfan']
