Provenge, a cancer vaccine, has demonstrated its ability to improve the survival of men with castrate resistant prostate cancer (CRPC). The developer, Dendreon, has submitted it latest clinical trial data to the FDA for approval. We hope to have an approval by mid-year 2010.

Growth factors were thought to be potential targets for treating prostate cancer. Unfortunately, tests have proven the agents targeting these factors have been ineffective. Monoclonal antibodies to block IL-6 have been developed but the trials have been stopped due to excessive toxicity.

Calcitriol, a form of vitamin D3, has been combined with docetaxel (chemotherapy) in a clinical trial. However, it showed more deaths in the combination arm and the trial was stopped.

Anti-clusterin agents (clusterin is a protein associated with the clearance of cellular debris and apoptosis) in combination with docetaxel have shown improved survival in a randomized phase II trial.

Atrasentan, and denosumab attack the bone environment, a primary target for prostate cancer.

A)- Atrasentan, an endothelin receptor antagonist improved bone pain but did not improve survival.

B) – Denosumab is designed to target Rankel Ligand, a protein that acts as the primary signal to promote bone removal (Proper bone health requires bone removal and bone replacemrnt to be in balance). A phase III trial involved 1,468 prostate cancer patients receiving hormone deprivation therapy (ADT), who were randomized to receive either denosumab or a placebo every 6 months over a 36 month period. All subjects also received supplemental calcium and vitamin D. Of those taking the placebo, 3.9% experienced bone fractures during the 36 months, compared with 1.5% of those who received denosumab The FDA delayed approval of denosumab in October 2009 because it wanted additional information about the drug.

ZD 4054 is a specific endothelian A inhibitor which when combined with docetaxel showed improved survival in phase II trials, but no difference in PSA response. Currently it is in phase III trials.

Docetaxel + bevacizumab (trade name Avastin), an anti-angiogenic agent, is being studied in CRPC and the results from a recently completed phase III trial is expected spring of 2010. Avastin recognizes and blocks vascular endothelial growth factors which serves as a chemical signal that stimulates the growth of new blood vessels to support tumors (angiogenesis).

Abiraterone and MDV 3100 are described as super androgen inhibitors by stopping androgen production in the testis, adrenals, and prostate. These agents are effective in chemotherapy naïve and resistant patients. A recently completed phase III trial evaluating abiraterone in CRPC who have failed docetaxel should report results soon.

Joel T Nowak MA, MSW