Most men with recurrent prostate cancer (CaP) initially respond to androgen 
deprivation therapy but eventually develop metastatic castration-resistant 
prostate cancer (CRPC). Over the last decade, new therapeutic targets have been 
identified in CRPC and several new drugs have reached advanced stages of 
clinical development. In 2010, the Food and Drug Administration (FDA) approved 
sipuleucel-T and cabazitaxel, and in 2011, abiraterone for patients with 
metastatic CRPC based on phase 3 trials showing improved survival. Although not 
yet available for clinical use, a press release in June 2011 announced that 
radium 223 also demonstrated a survival advantage in men with metastatic CRPC. 
Emerging therapies in advanced stages of clinical development in CRPC include 
the hormonal therapies MDV3100 and TAK 700, and the immunotherapy ipilimumab. 
Results are also pending on phase 3 studies comparing docetaxel plus prednisone 
with docetaxel given with the novel agents aflibercept, dasatinib, lenalidomide, 
and custirsen. In addition to these new and emerging therapeutic agents, 
denosumab was approved for the prevention of skeletal complications in patients 
with bone metastases due to solid tumor malignancies, providing an alternative 
to zoledronic acid. While the addition of these new treatment options is a great 
advance for men with metastatic CRPC, there are many new questions arising 
regarding sequencing of these treatments with each other, with previously 
existing therapies, and with the emerging agents now in clinical trials. 
Furthermore, there are concerns that on-going phase 3 trials may be contaminated 
if patients go off study treatment to start 1 of the newly approved agents or 
take the agent subsequently. These realities make clinical trial design more 
challenging than ever.