THE HYPERTEXT GUIDE TO PROSTATE CANCER



HORMONE THERAPY

FOR LATE-STAGE CANCER     FOR EARLY-STAGE CANCER     SIDE EFFECTS

Hormone therapy is used in three situations:

  • To slow down the spread of cancer cells that have escaped (secondary or adjuvant therapy).
  • To ease pain caused by the spread of the cancer (palliative therapy).
  • To shrink the prostate and the tumor before a procedure, in order to reduce the likelihood of escape (neoadjuvant therapy).

The therapy is known by many names, including:

androgen ablation
androgen deprivation
androgen suppression (AST)
combined hormone blockade (CHB)
combined hormone therapy (CHT)
endocrine therapy
hormone blockade (HB)
hormone therapy (HT)
neoadjuvant hormone blockade (NHB)
total androgen blockade (TAB)

They do not all necessarily involve the same drugs nor are they necessarily intended to achieve the same ends.

BLOCKING TESTOSTERONE: DRUGS

Hormone therapy works by blocking the production of androgens (male sex hormones).

LHRH analogs. The drugs used to block production of testosterone in the testicles are man-made hormones: luteinizing hormone-releasing hormone analogs, usually called LHRH or LH-RH. The drug is introduced in a series of one-, three-, or four-month injections of Zoladex (generic name goserelin) or Lupron (generic name leuprolide). There is also a one-year leuprolide-acetate implant called Viadur, which is used primarily for the palliative treatment of advanced prostate cancer. An estrogen-like drug called Diethylstilbestrol (DES) was formerly used in hormone blockade, but the side effects were found to be too dangerous.

Pharmaceuticals used to treat prostate cancer—an overview
Lupron, general information
Lupron, more specific information
Viadur
Zoladex, general explanation
Zoladex, warnings

Anti-androgens. The testosterone produced by the adrenal glands is blocked by an anti-androgen—usually Eulexin (flutamide), Casodex (bicalutamide), or Nilandron (nilutamide). It is taken daily in pill form. You should begin to take the anti-androgen about 10 days before the first shot of the LHRH agonist in order to avoid a temporary increase in testosterone. (See biochemical flare, next section.) Some doctors may prescribe Cytadren (aminoglutethamide) or Nizoral (ketoconazole) for late-stage treatment. Patients who take Cytadren or Nizoral must also take hydrocortisone pills.

Casodex (bicalutamide), general information
Casodex (bicalutamide), more specific
Casodex overview, fairly technical
Eulexin (flutamide)
Nizoral (ketoconazole)
Nilandron (nilutamide)

Physicians are divided over which of these drugs are superior. Because they are expensive, insurance companies and HMOs may not wish to pay for neoadjuvant treatment (or may balk at more than three months of neoadjuvant treatment). Zoladex and Eulexin are the less expensive.

Biochemical flare. It is extremely important to begin taking the anti-androgen (Eulexin, Casodex, Nilandron) ten days to two weeks before the first shot of the LHRH agonist (Zoladex, Lupron, Viadur). If the injection occurs at the same time or earlier, biochemical flare, a temporary increase in testosterone, will occur. This can prove very dangerous for some patients. (Many doctors do not seem to be aware of this.)

About biochemical flare

Side effects. All of these drugs have potential side effects. Some people may experience strong and even dangerous side effects. Read up on them before you ask your doctor to prescribe a course of hormone blockade.

List of side effects
Guide to cancer drugs
rxlist (drug information)

BLOCKING TESTOSTERONE: ORCHIECTOMY

A bilateral orchiectomy (castration) is the fastest and simplest way to block the testosterone production of the testicles. It is an outpatient operation that can be done under local anesthesia. A small incision is made in the front of the scrotum and the testicles are removed. This does not eliminate the testosterone produced by the adrenals, but that production appears to make little difference, according to a study of bilateral orchiectomy with or without flutamide. New England Journal of Medicine. 1998 Oct 8;339(15):1036-42. A quality of life and cost-effectiveness analysis that compared physical and chemical castration found that “Orchiectomy is the treatment of choice when life expectancy is more than two years.” Anticancer Research 2001 Jan-Feb;21(1B):781-8

Upside: If the cancer has already reached the bones, this is the quickest way to slow tumor growth and pain.Testosterone levels drop dramatically and the patient often has rapid relief from cancer symptoms. Orchiectomy is less expensive than chemical castration. Journal National Cancer Institute, Vol. 92, No. 21, 1731-1739

Downside: The operation is irreversible and, like all surgery, involves risks. It may require being hospitalized for approximately two days or more. The patient must deal with the psychological aspects of castration. Possible side effects include pain, constipation, urination problems, fatigue, and, of course, impotence and loss of sexual desire.

About orchiectomy
One patient's experience with orchiectomy

HORMONE BLOCKADE AND LATE-STAGE CANCER

Unfortunately, hormone therapy has its limits for late-stage patients. After a while, the cancer begins to grow again, a condition called becoming hormone-refractory. The cancer can then be slowed down again by stopping the hormone blockade, which seems to force the cancer cells to re-adapt. The blockade is resumed when the PSA begins to rise again, but doctors differ on what number the PSA should reach before treatment resumes. This is sometimes called intermittent hormone therapy.

A brief introduction to metastatic cancer

Bone metastasis. Escaped prostate-cancer cells often settle in the bones. These secondary tumors can cause changes in the bones that will weaken them or, by pressing against nerves as they grow, cause pain.

About bone metastasis

HORMONE BLOCKADE AND EARLY-STAGE CANCER

Many studies have shown that a few months of hormone therapy before treatment can shrink tumors significantly. Neoadjuvant hormone therapy (also called combined hormone therapy, androgen-deprivation therapy, and hormone blockade) employs the same drugs given to those who have advanced cancers. One drug, given by injection, suppresses the testosterone produced by the testicles, the other, taken orally, suppresses testosterone from the adrenal glands. The regression of tumors does not begin to occur until after the third month, so a treatment of only three months is unlikely to accomplish much. Journal of Urology 2001 Aug;166(2):500-506 This therapy by itself will not eradicate a tumor. Eventually, the cancer will adapt and resume growing.

Ideally, neoadjuvant therapy should be done under the supervision of the physician who will perform the treatment you have selected. If you have not yet chosen a treatment (or a physician), you can have your urologist determine the volume of your prostate and monitor the progress so that you can avoid reducing the size beyond that which is ideal for the procedure. (Neoadjuvant therapy is now standard treatment before radiation but not necessarily for surgery.)

Dr. Labrie's original study of neoadjuvant therapy
A detailed overview that cites various studies
Prostate volume

SIDE EFFECTS

The side effects of hormone blockade are the same for local and advanced cancers. Some of these may appear early on while others may only appear after a year or more of treatment.

LIST OF SIDE EFFECTS

alcohol intolerance (with Casodex and Eulexin)
anemia
anxiety or depression
arthritic symptoms
appetite loss
blood in urine
breasts, swelling of
(gynecomastia—see below)
cholesterol and triglycerides increase
constipation
diarrhea
(with Eulexin)
disturbed sleep
drowsiness
dry mouth
emotional instability
(especially crying)
feet or lower legs, swelling of
(peripheral edema)
flatulence
flu syndrome
hair change
(decrease in pubic and axillary hair; facial hair grows more slowly)
headache
high blood pressure
(hypertension)
hot flashes
hyperglycemia
(high blood sugar)
impotence
(during the period of treatment and for some months after)
indigestion
itching
insomnia
liver problems
memory loss
methemoglobinemia
(a crystalization in the blood)
nausea
nocturia
(need to urinate frequently at night)
nervous and twitchy legs
osteoporosis
pain: abdominal, back, chest, in right side
pressure: feeling of extreme pressure in head
prickling sensation on the skin
shortness of breath
testicular soreness; atrophy
(shrinking)
sweating
weight gain
(may continue for a while after treatment)
weight loss

The following symptoms may reflect serious problems.
Contact your doctor immediately.

abdominal pain*
anorexia* (persistent appetite loss)
bluish lips, fingernails, or palms of hands
dark urine (may reflect hyper bilirubinuria)*
dizziness (extreme) or fainting
fatigue, weakness
flu-like symptoms*
infections
itching, severe (pruritus)*
nausea*
numbness, coldness, or tingling of hands or feet
pain: bone, joints, pelvic
rash
tenderness on the right side of the upper abdomen*
urinary incontinence
urinary tract infection
vomiting*
weak and fast heartbeat
yellow eyes or skin*

* These may indicate liver-function problems. See liver problems, below.


Click here to download the side-effects information as a one-page pdf file

DEALING WITH SIDE EFFECTS

Liver problems. Eulexin (flutamide) and Nizoral (ketoconazole) may cause liver problems, so a liver-function-monitoring blood test (measuring serum transaminase levels) should be performed before beginning this treatment, repeated monthly for the first four months, and periodically thereafter during the treatment. Patients whose ALT values exceed twice the upper limit of normal should not begin flutamide. Evidence of hepatic injury may include elevated serum transaminase levels, jaundice, and hepatic encephalopathy. Death may occur as a result of acute hepatic failure. Injury may be reversible if treatment is immediately discontinued.

Warning about Eulexin (flutamide)
Eulexin (flutamide)
Nizoral (ketoconazole)

Testosterone levels. Another blood test should be made to ensure that testosterone has reached a minimal level (“castrate level”). The definition of castrate level is not the same with every test.

Anemia. This may be avoided with careful eating habits. It can also be treated by your doctor.

Anemia, basic definition

Temporary impotence and elimination of sexual drive. Unfortunately, there is nothing that can be done about this. Some men report that they do not lose their sexual drive, but this may be a sign that the treatment is not working as it should.

Gynecomastia. In an email to P2P, Dr. Barken wrote: “I think it is a good idea to take two days of radiation to the breast tissue. It is very safe and effective to avoid the problem of enlargement and tenderness of the breast.” Gynecomastia may resolve itself in time. If not, plastic surgery may be the only way to correct this condition.

About gynecomastia
About gynecomastia, several accounts

Hot flashes (also called hot flushes). Some men (and women) report that drinking soy milk helps reduce these. Megace may work, but its side effects can be worse than the hot flashes. Check with your doctors before trying anything.

Depo-Provera (medroxyprogesterone)
Megace for hot flushes

Memory may improved by prescription drugs. Some patients report that gingko biloba, available in health-food stores, is helpful. Check with your doctors before you use it because it may conflict with other medicines.

Muscle loss can be avoided through exercise and weight lifting.

Osteoporosis and arthritis may be prevented and treated with bisphosphonate compounds, calcium citrate supplements, exercise and vitamin D, as prescribed by your doctor. Osteoporosis is the loss of large amounts of bone. The weakening of the bones can cause fractures to occur.

Osteoporosis overview
Bone density test

Download the side-effects information as a one-page pdf file

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