Hormonal Therapy in Prostate Cancer

Dr.Ahmad Kharrouby

Androgen deprivation induces a remission in 80 to 90 percent of men with advanced prostate cancer

And results in a median progression-free survival of 12 to 33 months

Indications

Metastatic Prostate Cancer In recurrence after XRT or Surgery, most

patients receive androgen ablation therapy Most patients with T3 are, at the present

time, treated with neoadjuvant hormonal therapy followed by XRT

Nobel Prize

The scientist Charles Huggins first established this over 60 years ago in work that led to his winning the Nobel Prize

Huggins found that Bilateral orchiectomy could slow the growth of the disease

Androgens Sources

About 90% to 95% of all androgens are made in the testicles

While the rest are made in the adrenal glands

How Does Hormone Therapy Work?

By either:– Preventing the body from making these

androgens – Or by blocking their effects

In what Percentage?

In 85% to 90% of cases, it can shrink the tumor

However, hormone therapy for prostate cancer doesn't work forever

What Types of Hormone Therapy Are There?

There are two basic kinds:– One class of drugs stops the body from making

these hormones– The other blocks its effects

Some start treatment with both to achieve a total androgen block, but it is not the rule

Here's a rundown of the techniques

LHRH Agonists

The inhibitory action is due to a combination of receptor down-regulation and changes in the signaling pathways activated by GnRH

During the first 7–10 days, serum testosterone levels increase

Within about 2 weeks, serum testosterone levels fall to the hypogonadal range

Most LHRH agonists are injected every one to four months

Some examples are Lupron, Trelstar, Vantas, and Zoladex

A new drug, Viadur, is an implant placed in the arm just once a year

LHRH Agonists

Side effects can be significant. They include: – Loss of sex drive– Hot flashes– Development of breasts (gynecomastia)– Loss of muscle– Weight gain– Fatigue– Decrease in levels of HDL

Anti-androgens

LHRH agonists and orchiectomies only affect the testicular androgens

Thus they have no effect on the 5% to 10% that are made in the adrenal glands

Anti-androgens are designed to affect the hormones made in the adrenal glands

The advantage of anti-androgens is that they have fewer side effects than LHRH agonists

Many men prefer them because they are less likely to diminish libido

Taken as pills each day Examples are Casodex, Eulexin, and Nilandron

In some cases, starting treatment with an LHRH agonist can cause a "tumor flare," a temporary acceleration of the cancer's growth due to an initial increase in testosterone before the levels drop

This may worsen symptoms Thus starting with an anti-androgen drug and then switching to

an LHRH agonist can help avoid this problem

Strangely, if treatment with an anti-androgen doesn't work, stopping it may actually improve symptoms for a short time

This phenomenon is called "androgen withdrawal," and experts aren't sure why it happens

Combined Androgen Blockade

This approach combines anti-androgens with LHRH agonists or an orchiectomy

By using both approaches, you can cut off or block the effects of hormones made by both the adrenal glands and the testicles

However, using both treatments can also increase the side effects

Estrogens

In fact, they were one of the early treatments used for the disease

However, because of their serious cardiovascular side effects, they're not used as often anymore

Examples of estrogens are DES (diethylstilbestrol), Premarin, and Estradiol

Other Drugs

Proscar (finasteride) Nizoral (ketoconazole) Cytadren (aminoglutethimide)

Orchiectomy

The surgical removal of the testicles was the earliest form of hormone therapy for prostate cancer

As with LHRH agonists, side effects can be significant

However, it can be the right choice in certain cases– Non compliant men– Non sexually active men– Financial reasons

Hormone therapy for prostate cancer can cause osteoperosis

However, treatment with bisphosphonates -- like Aredia, Fosamax, and Zometa -- may help prevent this condition from developing

What Type of Hormone Therapy Works Best?

LHRH agonists remain the usual first treatment But in some cases, doctors are trying anti-androgens

first Anti-androgens may be especially appealing to

younger men who are still sexually active Others prefer to begin therapy with a combination of

two or even three drugs, especially for patients with symptoms or advanced disease

Some studies have shown slightly longer survival with combined androgen blockade, but the results haven't been encouraging

Different Approaches to Starting Hormone Therapy

Experts debate how early treatment with hormone therapy should be started

Some argue that the benefits of hormone therapy for prostate cancer should be offered to men earlier in the course of the disease

Others assert that there's little evidence that getting treatment early is better than getting it later, especially that these drugs have serious side effects

Thank you