Hormone Therapy for Prostate Cancer

Most prostate cancers require testosterone in order to survive and thrive. Prostate cancers which are dependent on testosterone are called 'androgen sensitive'. Those which no longer require testosterone to grow are known as 'androgen insensitive' or 'castrate resistant'. Some of this terminology is changing since it is now realized that some tumors which continue to grow despite 'castrate' levels of testosterone are, in fact, still sensitive to hormonal manipulation.

 

Rising PSA + Low Testosterone = Castrate-Resistant Prostate Cancer

 

Withdrawal of testosterone most commonly will put prostate cancer into remission and in some cases can enhance the curative effects of other treatments, most specifically radiation. The use of LHRH agonists has been of no benefit prior to surgical treatment, however. Testosterone withdrawal in and of itself, however, is incapable of curing prostate cancer.

 

Classes of Hormonal Therapy for Prostate Cancer

 

IMPORTANT: These medications can only be picked up at the BC Cancer Agency Pharmacies. The cost is covered under routine Pharmacare coverage.

 

Hormonal therapy takes many different forms. When it was first discovered that prostate cancer could be controlled with androgen deprivation in the 1950s, the initial treatment modality was surgical castration (removal of the testes). Since that time, alternative medical treatments have become the main stay of hormonal therapy and surgical castration is much less commonly performed. "Medical castration" can be undertaken with many different types of medication which can be classified as follows:

 

Antiandrogens

Antiandrogens block the testosterone receptor. Unlikely LHRH agonist, they do not decrease testosterone production. some of these medications also maintain some progestin-type activity and are known as 'steroidal anti-androgens'. All of these medications are administered by mouth.

 

Examples and dosages:

Flutamide (Eulexin) 250 mg three times per day

Bicalutamide (Casodex) 50 mg daily

Nilutamide (Andron) 100mg daily

Cyproterone acetate (Androcur) 100 mg twice daily

LHRH Agonists

Luteinizing Hormone Releasing Hormone agonists suppress testicular testosterone production by interfering with the normal pulsatile release of gonadotropin releasing hormone. After an initial increase in testosterone production for the first one to 2 weeks, testosterone production is suppressed. These medications are sometimes initially paired with an antiandrogen and patients who have high-risk features.

 

These are all administered as injections, either into the fat or muscle. The dosing is typically every one to 3 months, but quite often do not need to be given as frequently with injections every 3-5 months commonly being sufficient. The goal of these medications is to fully suppress testosterone levels. So long as the testosterone is fully suppressed (i.e. less than 0.5 nmol/L), then a repeat injection may not be necessary.

 

Examples and dosages (trade name in brackets):

Goserelin (Zoladex) 10.8 mg subcutaneously every 3 months

Leuprolide (Lupron) 22.5 mg intramuscularly every 3 months

Leuprolide (Eligard) 22.5 mg subcutaneously every 3 months or 30 mg subcutaneously every 4 months

Buserelin (Suprefact) 9.45 mg subcutaneously every 3 months

 

The Others

There are a number of other potential sources for androgen production. These include the adrenal gland and in some circumstances prostate cancer cells can develop the ability to synthesized testosterone themselves (independent of the testes or adrenal glands).

 

Ketaconazole: inhibits synthesis of all testosterone, including in the adrenal glands. Typical dosing is 400 mg three times a day; supplementation with low dose prednisone.

Abiraterone (Zytiga): inhibits testosterone and other steroid production atht eh CYP17A1 enzyme level. Approved for use in castrate-resistant prostate cancer. Inhibits synthesis of testosterone by all cells, including cancer cells. Side effects include: high blood pressure, low potassium and fluid retention wihch can be significantly reduced by using predisone. Typical dosing for abiraterone is 1000 mg (4 x 250 mg tablets) daily with prednisone 5 mg twice daily.

 

Use of Hormonal Therapy in Prostate Cancer

 

Just as for any other treatment for prostate cancer, whether or not hormonal therapy is right for your disease depends on your particular circumstances. in general, hormonal therapy is used either as an adjunct to curative therapy (most importantly radiation) or in the palliative treatment of incurable disease. In either circumstance, the decision to use any treatment is based on the balance of potential harms and benefits of these medications. The potential benefits are quite obvious in terms of increasing the chances of cure, relief or delay of onset of symptoms and potentially prolongation of life. Potential adverse effects of hormonal therapy include things such as osteoporosis, loss of muscle mass, fluid retention, hot flushes, et cetera.