A new hormonal therapy for castration resistant prostate cancer

This early phase study assessed the efficacy and safety of a new drug, Orteronel (TAK-700), in patients with castration-resistant prostate cancer.

Androgen deprivation therapy (ADT), or castration therapy, is the standard of care for advanced prostate cancer. ADT usually involves either surgical castration (surgical removal of the testicles) or medical castration (hormonal therapy), intended to reduce the production of androgens (male sex hormones such as testosterone), or inhibit their effect on cancer cell growth. However, patients eventually become resistant to androgen deprivation and cancer growth and spread progresses despite treatment, often referred to as castration-resistant prostate cancer.

Due to the inevitable resistance of prostate cancer to androgen deprivation, recent research has focused on additional hormonal therapies that may further delay cancer progression and extend survival. Orteronel (TAK-700) is a newly developed anti-androgen drug that selectively inhibits an important protein responsible for the production of testosterone. These early phase trials assessed the safety and efficiency of this new hormonal agent.

A phase I study of TAK-700 enrolled 26 patients with metastatic castration-resistance prostate cancer. Men were treated with various dosages of orteronel. 12 weeks into treatment, 65% of patients showed significant reductions (of 50% or greater) in PSA levels (prostate-specific antigen; a protein produced by prostate cells and when elevated indicates growing prostate cancer). However, 31% of patients experienced serious adverse effects.

In a phase II study, 97 patients with metastatic castration-resistance prostate cancer were randomly assigned to receive either orteronel alone, or orteronel in combination with prednisone (a steroid drug used to suppress the actions of the immune system). At 12 weeks, 54% of patients completing treatment experienced a significant decline in PSA levels. At 24 weeks, 63% of patients completing treatment experienced a significant decline in PSA levels. However, 53% of the patients experienced adverse events due to treatment, including 27% of patients experiencing severe adverse events.

This study concluded that orteronel, with or without the addition of prednisone, effectively reduces PSA levels among castration resistant prostate cancer patients.

These early phase trials included only a small number of patients. Late-phase, large, controlled studies are necessary to confirm the benefits of orteronel.

Millennium pharmaceuticals, which manufactures Orteronel (TAK-700), funded these trials.

Consult with your physician regarding the risks and benefits of orteronel in the treatment of castration-resistance prostate cancer.