Combination Therapies in Clinical Trials for Advanced Prostate Cancer

In a recent interview, Dr. Mario Eisenberger, Professor of Urology and oncology at Johns Hopkins, summarized a group of on-going clinical trials for patients with metastatic, hormone-resistant prostate cancer.  Trials are ongoing combining agents targeting the androgen receptor such as abiraterone (Zytiga®) with chemotherapies such as docetacel® (taxotere) or cabazitaxel (Jevtana®). Other trials such as the Alliance trial, combines abiraterone with enzalutamide (Xtandi®).  An on-going phase III trial combines abiraterone with radium -223 (alpha-radin, Xofigo®) in men with metastaic disease who have not received chemotherapy.  Dr. Eisenberger states that there are a number of trials combining approved drugs with chemotherapy and hormonal therapy and radiopharmaceuticals such as radium-223.  There are also trials using combinations of PARP inhibitors (s0 far un-approved for prostate cancer) with standard, second line hormonal therapies. Also there are antitumor PI3K  and AKT inhibitors some of which inhibit more than one pathway which are over-expressed in prostate cancer patients who progress on androgen receptor-targeted compounds such as abiraterone or enzalutamide.  The question is whether PI3K or AKT inhibitors will enhance the effects of abiraterone or enzalutamide.  Dr. Eisenberger also discusses trials involving approved agents for metastatic disease as well as unapproved agents like TAK-700 (Ortoronel®) and ARN509 being tested in men with metastatic, hormone-naive cancer.  In addition, chemotherapy trials such as CHAARTED and STAMPEDE are discussed.  This post is primarily aimed at physicians.  If you are a patient with metastatic disease, I suggest you discuss these trials with your physician to see if any one would apply to your specific situation.