Document Detail

Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma.
MedLine Citation:
PMID:  23151808     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Src 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 METHODS: We 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.
RESULTS: Twenty-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.
CONCLUSIONS: Saracatanib 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.
Tara C Gangadhar; Joseph I Clark; Theodore Karrison; Thomas F Gajewski
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural     Date:  2012-11-15
Journal Detail:
Title:  Investigational new drugs     Volume:  31     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-06     Completed Date:  2013-11-26     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-73     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Antineoplastic Agents / pharmacology,  therapeutic use*
Benzodioxoles / pharmacology,  therapeutic use*
Interleukin-2 / immunology
Melanoma / drug therapy*,  immunology,  pathology
Middle Aged
Neoplasm Metastasis
Protein Kinase Inhibitors / pharmacology,  therapeutic use*
Quinazolines / pharmacology,  therapeutic use*
T-Lymphocytes / drug effects,  immunology
Treatment Outcome
src-Family Kinases / antagonists & inhibitors*
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzodioxoles; 0/Interleukin-2; 0/Protein Kinase Inhibitors; 0/Quinazolines; 9KD24QGH76/saracatinib; EC Kinases

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