The Prostate
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Comparative Study
Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone.
The optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone. ⋯ Treatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.
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Chemokines and cytokines have been implicated in progression to castration-resistant prostate cancer (CRPC). ⋯ Higher levels of inflammation-associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy.
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Multiparametric magnetic resonance imaging (mpMRI) is the standard for local prostate cancer (PCa) staging. Whole-body MRI (wbMRI) has shown capabilities for metastatic screening. This study assesses the feasibility and value of an all-in-one AJCC TNM staging of PCa during a unique MRI session combining mpMRI and wbMRI. ⋯ AJCC M and N staging using wbMRI is feasible during the same imaging session as mpMRI performed for T staging, in less then one hour. wbMRI outperforms BS ± TXR and abdomino-pelvic CT work up for discriminating subsets of patients with or without distant spread of the cancer.
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Insulin-like growth factor (IGF) and adipokines have been implicated in prostate cancer carcinogenesis. ⋯ Elevated IGFBP-1 appears to be associated with shorter time to CRPC and lower overall survival in men with metastatic prostate cancer.
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Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: binding of androgens to AR, AR nuclear translocation, and association of AR with DNA. Here, we investigate the effects of enzalutamide on AR signaling, AR-dependent gene expression and cell apoptosis. ⋯ These results indicate that enzalutamide efficiently inhibits AR signaling, and we suggest that its lack of AR agonist activity may be important for these effects.