Background Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor–signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy. Methods In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival. Results The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for de...

/pdf/increased-survival-with-enzalutamide-in-prostate-cancer-1v77512mc7.pdf

Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

Androgen receptors in hormone-dependent and castration-resistant prostate cancer.

Signaling networks play key homeostatic processes in living organisms but are commonly hijacked in oncogenesis. Prominent examples include genetically altered receptor tyrosine kinases and dysregulated intracellular signaling molecules. The discovery and development of targeted therapies against such oncogenic proteins has imparted clinical benefit. Nevertheless, concerns remain about the limited single-agent efficacy and narrow therapeutic indices of many of these antitumor agents. Moreover, it is apparent that oncogenic proteins comprise complex signaling networks that interact through crosstalk and feedback loops, which modify therapeutic vulnerability. These complexities mandate the study of drug combinations, which will also become necessary to reverse tumor drug resistance. Here, we outline the challenges associated with rational drug codevelopment strategies, with a focus on the importance of analytically validated biomarkers for patient selection and pharmacokinetic-pharmacodynamic (PK-PD) studies...

Development of Therapeutic Combinations Targeting Major Cancer Signaling Pathways

Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone.

Molecular Pathogenesis and Progression of Prostate Cancer

We read with interest the report from Richards and colleagues ([1][1]) on the potential interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor (AR). Abiraterone is a CYP17A1 inhibitor that blocks androgen biosynthesis in the testes, adrenals, and

http://cancerres.aacrjournals.org/content/canres/73/9/2926.full.pdf

Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-Type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100—Letter

Resident Education and Management of End-of-Life Care: The Resident's Perspective

Nocturia is common in middle-aged and older patients, affecting 40–60% of people > 55 years old [1-3]. It is classically considered to be a urological disorder, whereby excess production of urine at night, or a reduced nocturnal bladder capacity, leads to an awakening to void. An alternative possibility is that sleep disruption, a common feature of aging [4-6], leads to a nocturnal awakening and a decision to void. To explore the associations between urinary symptoms, sleep disruption and daytime sleepiness, we conducted a survey in two groups of older adults: patients visiting our urology clinic and healthy adults volunteering for sleep or circadian rhythm studies in our research laboratory.

/pdf/reciprocal-relationship-between-age-related-sleep-disruption-46iywauqu2.pdf

Reciprocal relationship between age-related sleep disruption and urological symptoms

784 the impact of abiraterone acetate therapy on patient-reported pain and functional status in chemotherapy-naïve patients with progressive, metastatic castration-resistant prostate cancer - results from an updated analysis

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Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-Type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100—Letter

Resident Education and Management of End-of-Life Care: The Resident's Perspective

Reciprocal relationship between age-related sleep disruption and urological symptoms

784 the impact of abiraterone acetate therapy on patient-reported pain and functional status in chemotherapy-naïve patients with progressive, metastatic castration-resistant prostate cancer - results from an updated analysis