Prostate Cancer Hormone Therapy Drugs

The standard treatment options for prostate cancer (PC) include hormone-based therapy, surgery, radiotherapy/chemotherapy and active surveillance (PSA measurements). The aim of PC hormone drug therapy is to prevent the production, directly or indirectly, of androgens, the male steroid hormones, and to block their action using two classes of drugs. Referred to as complete androgen blockade (CAB) or androgen deprivation therapy (ADT), this strategy involves inducing chemical castration, a therapeutic approach that significantly enhances survival in patients. In the 2007 Journal of Urology, Dr. Michael Brawer presents 10 steps when advising patients about initiating hormone therapy in prostrate cancer.

Hormone Therapy in Prostate Cancer: Complete Androgen Blockade (CAB)

• CAB is achieved by inhibiting androgen synthesis through feedback inhibition of the hypothalamic pituitary gonadal axis while also using a conventional anti-androgen drug to prevent androgens from binding to the androgen receptor (AR) in the prostate. These two distinct methods limit tumor growth in PC and consist of the gonadotropin releasing luteinizing hormone (GnRH or LHRH) analogs, which induce chemical castration by lowering testosterone production by the testes, and the conventional anti-androgens, which block the AR from being activated.

GnRH/LHRH Agonists & Antagonists (Chemical Castration)

• The GnRH/LHRH agonists and antagonists have provided successful androgen-deprivation therapy (ADT). Degarelix and abarelix are GnRH/LHRH antagonist for the treatment of patients with advanced prostate cancer. Histrelin acetate is the only GnRH/LHRH agonist that is available as a once-yearly implant (Vantas). Leuprolide, goserelin and triptorelin are other agents used via injection. LHRH agonists lupron, zoladex, eligard, viadur, trelstar or vantas, and the LHRH antagonist plenaxis, are brand names within this category of hormone treatment.

Conventional Anti-Androgen Treatment

• The direct anti-androgen therapies include bicalutamide (casodex), nilutamide (anandron) and flutamide (eulexin), which bind to the AR and block testesterone or other androgens from perpetuating tumor growth. Finasteride (Proscar), targets the enzyme that converts testosterone to dihydrotestosterone (DHT), which is the most potent male steroid hormone; blocking its formation significantly attenuates tumor growth. Finasteride is now being considered for prophylactic long-term treatment. Studies have shown it lowering PC risk by up to 30 percent in the short term, however high-grade tumors were more prevalent with long-term Finasteride treatment. Additional hormone therapies include diethylstilbestrol, a synthetic estrogen that demonstrates efficacy in treating advanced PC through hormonal manipulation.

Hormone-Resistant/Refractory Prostate Cancer: Castration-Resistant Prostate Cancer

• Castration or hormone-resistant prostate cancer (CRPC/HRPC) is a refractory state that does not adequately respond to hormone treatment. It is a very aggressive disease with limited treatment options. Standard treatment consists of castration-using GnRH/LHRH agonists and antagonist in combination with docetaxel-containing chemotherapy, along with other regimines implemented to palliate symptoms. Orchiectomy (surgical castration) is also a form of hormone therapy by which the primary source of androgen in the body, the testes, are removed.

Combination Hormone Therapy

• The growth of PC is dependent on testosterone and other potent androgens, especially prior to advanced stages of the disease. The goal of hormone-based treatments is to reduce the level of androgen circulating in the body, with the intent to sustain, castrate or lower levels. Hormone-based therapy generally involves one (monotherapy) or more (dual or combination therapy) of the agents listed, often a GnRH/LHRH agonist/antagonist in conjunction with an anti-androgen. Overall, this mode of therapy has proved significant in reducing the mortality rates associated with prostate cancer.