Novel Therapies for Castration-Resistant Prostate Cancer

The present article reviews new and prospective treatments for castration-resistant prostate cancer (CRPC). Sipuleucel-T, Cabazitaxel, Denosumab and Abiraterone are novel therapies approved in the last few years for CRPC, while several other therapeutic agents such as MDV3100, Alpharadin and Cabozantinib are currently under development.

Advanced prostate cancer that has spread to distant organs (metastatic) and has become irresponsive to hormonal therapy is regarded as CRPC. Such patients are usually offered chemotherapy as last resort, to which CRPC may stop responding as well.

Recently (2010-2011), several new therapies were approved for CRPC treatment:

Sipuleucel-T (PROVENGE) was approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic CRPC. In 225 CRPC patients (who did not receive prior chemotherapy) Sipuleucel-T was shown to reduce mortality by 33%. In another study, Sipuleucel-T prolonged the median survival of 512 CRPC patients with 4 months compared with placebo.

Cabazitaxel (JEVTANA) was approved for use in combination with a steroid (Prednisone) for the treatment of metastatic CRPC that failed on treatment with another chemotherapeutic drug called Docetaxel. Cabazitaxel improved overall survival with approximately 3 months compared with another chemotherapeutic agent (Mitoxantrone).

Abiraterone (ZYTIGA) was approved for use with Prednisone for the same indication as Cabazitaxel. This combined treatment prolonged the overall survival in 1195 Docetaxel-resistant CRPC patients in comparison to those receiving Prednisone only (14.8 months versus 10.9 months).

Denosumab (PROLIA, XGEVA) was approved for the prevention of skeletal-related events (fractures orthopedic surgery) in patients with bone metastases. Denosumab prolonged the median time to induce skeletal-related events when compared with standard therapy (20.7 months versus 17.1 months) in 1904 CRPC patients.

Among the new therapies under development, MDV3100 (Enzalutamide) significantly reduced post treatment prostrate-specific antigen (PSA) levels and demonstrated a 37% reduction in the risk of death in 1199 CRPC patients. Treatment with Alpharadin prolonged overall survival with 3 months compared to placebo in 922 CRPC patients with bone metastases.

Since multiple therapeutic options with diverse mechanisms of action are available now, appropriate selection and timing of therapies is needed. Also, while combining multiple treatments, compatibility of the drugs with one another should be evaluated for effective and safe treatment of CRPC.