More effective androgen blockade possible?

This study examined the effectiveness of combined androgen blockade in the treatment of prostate cancer.

Prostate cancer is often dependent on androgens (male hormones such as testosterone, DHEA-S and andosterone) for growth. Therefore, the mainstay of prostate cancer treatment is androgen deprivation therapy, consisting of drugs which block the production of, or the ability of the body to use, androgens. However, small amounts of androgens remain present even among men undergoing androgen deprivation, which may contribute to cancer recurrence. Several new drug combinations are currently being investigated in an attempt to achieve a more effective blockade of androgen production. Goserelin (Zoladex) is considered the standard of care in androgen deprivation. Additional commonly prescribed androgen production inhibitors investigated include dutasteride (Avodart), ketoconazole (Nizoral), bicalutamide (Casodex).

35 patients diagnosed with local prostate cancer were randomly assigned to one of three combination androgen blockade treatments before undergoing surgery to remove the prostate. Group 1 received goserelin in combination with dutasteride. Group 2 received a combination of goserelin, dutasteride, and bicalutamide. Group 3 received a combination of goserelin, dutasteride, bicalutamide, and ketoconazole. Androgen levels were compared between treatments groups and against control patients receiving standard therapy with goserelin and bicalutamide.

Patients in any of the treatment groups showed greater declines in androgen levels compared to patients in the control group. Compared to control patients, who experienced a 68% decrease in total androgen levels, patients receiving goserelin with dutasteride saw an 88% decrease in androgen levels throughout treatment. Patients receiving goserelin, dutasteride, and bicalutamide saw a decrease of 86% in androgen levels throughout treatment. Patients receiving goserelin, dutasteride, bicalutamide, and ketoconazole saw a total decrease of 83% in androgen levels throughout treatment. Patients receiving this quadruple combination also experienced the greatest range of androgen deprivation, showing reductions in multiple androgen hormone levels including a 97% decrease in testosterone levels, a 67% decrease in DHEA-S levels and an 81% decrease in andosterone levels.

This small pilot study concluded that the use of additional androgen production inhibitors, such as dutasteride and ketoconazole, achieves a more effective androgen blockade beyond that reached by standard therapy.

This study only addressed androgen levels during treatment, without conducting a long-term analysis of cancer outcomes such as recurrence or survival.

Consult with your physician regarding the use of various androgen deprivation combinations in the treatment of prostate cancer.