New drugs change treatment landscape for advanced prostate cancer

Several drugs approved over the past two years for the treatment of prostate cancer plus others in the pipeline present the real possibility of prolonging survival for patients.

“The development and approval of these agents has generated an unprecedented excitement in prostate oncology,” wrote E. David Crawford, MD, and Thomas W. Flaig, MD, both from the University of Colorado Cancer Center and the University of Colorado School of Medicine in Aurora, in the journal Oncology.

As the authors noted in their review article, gonadotropin-releasing hormone (GnRH) agonists and anti-androgens were approved back in the 1980s, and docetaxel, which was approved for the treatment of prostate cancer in 2004, has been the only modern chemotherapy drug to demonstrate an overall survival advantage for men with castration-resistant prostate cancer (CRPC). Now, however, the arsenal for advanced prostate cancer includes sipuleucel-T (Provenge), cabazitaxel (Jevtana;), and abiraterone acetate (Zytiga), which were approved by the FDA in April 2010, June 2010, and April 2011, respectively, due to their ability to prolong overall survival in men with CRPC.

Crawford and Flaig also lauded denosumab, which was approved in November 2010 for prevention of skeletal-related events in patients with bone metastases from solid tumors and has been shown to hold off the occurrence of bone metastasis for an average of 4 months in men whose spiking prostate-specific antigen (PSA) scores predict the likely onset of bone involvement.

In addition, the reviewers described several promising agents for prostate cancer treatment that are in late-stage development, including:

  • MDV3100, a new-generation anti-androgen
  • PROSTVAC-VF (Prostvac), a PSA-targeted immunotherapy
  • Orteronel (TAK-700), a selective 17,20-lyase inhibitor similar to abiraterone that allows for a more targeted inhibition of CYP17, a key driver of testosterone production
  • radium-223 chloride (Alpharadin), a radiopharmaceutical for the treatment of bone metastases that uses alpha rather than beta particles; alpha particles can deliver radiation in a more localized way, with the potential for less bone marrow toxicity.

Crawford and Flaig advised that future trials be focused on defining the optimal application and timing of the four new therapies as well as the drugs being developed. “Theoretically, active agents in prostate cancer with the least amount of toxicity should be used earliest in the disease process,” they pointed out.

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