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
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