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• W1982827319 endingPage "477" @default.
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• W1982827319 abstract "Abstract Elevated levels of clusterin ( CLU ), a stress‐induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second‐generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second‐line chemotherapy in men with metastatic castration‐resistant prostate cancer ( mCRPC ) who had progressed while on or within 6 months of first‐line docetaxel‐based chemotherapy. Exploratory analyses evaluated serum CLU levels during custirsen treatment and correlative clinical effects on prostate‐specific antigen ( PSA ) response, overall survival, and any relationship between serum CLU and PSA . Men with mCRPC were treated with mitoxantrone/prednisone/custirsen ( MPC , n = 22) or docetaxel retreatment/prednisone/custirsen ( DPC plus DPC ‐Assigned, n = 45) in an open‐label, multicenter study. Subject‐specific profiles of PSA and serum CLU levels during treatment were characterized using statistical modeling to compute subject‐specific summary measures; these measures were analyzed for relationship to survival using proportional hazard regression. Estimated individual serum CLU response profiles were scored as below or at/above the median level for the population through 100 days postrandomization. Median survival was longer for subjects scoring below the median serum CLU level compared with subjects at/above the median level, respectively ( MPC : 15.1 months vs. 6.2 months; DPC ‐Pooled: 17.0 months vs. 12.1 months). Lowered serum CLU levels during custirsen treatment when in combination with either chemotherapy regimen were predictive of longer survival in mCRPC . These results support further evaluation of serum CLU as a therapeutic biomarker." @default.
• W1982827319 created "2016-06-24" @default.
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• W1982827319 date "2013-05-28" @default.
• W1982827319 modified "2023-10-17" @default.
• W1982827319 title "Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration‐resistant prostate cancer treated with custirsen" @default.
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• W1982827319 doi "https://doi.org/10.1002/cam4.93" @default.
• W1982827319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3799281" @default.
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