A Phase II Trial of Saracatinib, an Inhibitor of src Kinases, in Previously-Treated Advanced Non–Small-Cell Lung Cancer: The Princess Margaret Hospital Phase II Consortium

2区 · 医学

Article

作者: Schwock, Joerg ; Wright, John J ; Oza, Amit ; Laurie, Scott A ; Philip, Lindsay ; Nicholas, Garth ; Hirsh, Vera ; Goss, Glenwood D ; Tsao, Ming-Sound ; Reaume, M Neil ; Wang, Lisa ; Shepherd, Frances A ; Leighl, Natasha B

BACKGROUNDThe src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC.PATIENTS AND METHODSEligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients.RESULTSThirty-seven patients received a median of 2 cycles (range, 1-14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed.CONCLUSIONSThere may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered.

2013-06-01·Investigational New Drugs3区 · 医学

Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma

3区 · 医学

Article

作者: Tara C. Gangadhar ; Theodore Karrison ; Thomas F. Gajewski ; Joseph I. Clark

BACKGROUNDSrc kinases are activated in melanoma, and inhibition of Src kinase activity has pre-clinical anti-tumor effects. Targeting this pathway could therefore have therapeutic activity in patients with metastatic melanoma.PATIENTS AND METHODSWe conducted a multi-center, open-label study of the Src kinase inhibitor saracatanib (AZD0530) in patients with metastatic melanoma. Twenty-three patients received saracatanib at a dose of 175 mg daily. The primary objectives were to determine whether this agent had clinical activity in patients with advanced melanoma and whether it increased progression free survival. Functional effects on circulating T cells were also assessed.RESULTSTwenty-three patients received oral saracatanib on a continuous daily dosing regimen. There were no objective clinical responses. Saracatanib was generally well tolerated with few grade 3-4 adverse events. T cell function was inhibited in most patients, based on decreased superantigen-induced IL-2 production in post- versus pre-treatment samples.CONCLUSIONSSaracatanib has minimal clinical activity as a single agent in an unselected population of patients with advanced melanoma, as evidenced by a lack of objective responses in this study. Reduced T cell cytokine production in most treated patients suggests potential immune suppressive activity by this agent.

100 项与 saracatanib 相关的药物交易

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