Abstract

TPS249 Background: Currently, the survival of men who have failed docetaxel-based chemotherapy for metastatic CRPC is poor, on the order of 12-14 months, and for men with an elevated CTC count, this figure is even further reduced. Two of the principal molecular mechanisms of progression to the castrate-resistant state include loss of the PTEN tumor suppressor pathway and alterations in androgen receptor signaling through mutation or amplification. These pathways contribute to increased PI3K/mTOR signaling and AR-dependent signaling, respectively, which leads to progressive tumor growth, survival, treatment resistance, and metastasis. Based on this rationale, we are conducting a single arm phase II study of the mTOR inhibitor temsirolimus (Torisel) in combination with anti-androgen therapy, in order to assess the clinical activity of this combination on disease progression and changes in PSA and CTC counts. This trial is funded by the NCCN. Methods: Eligible men will have metastatic progressive CRPC based ...

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