Who Are Good Candidates

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The best candidates for hormone therapy are men whose prostate is large or whose cancer has spread locally, beyond the prostate. This treatment is also used for men whose cancer has spread distantly to bones (see Chapter 11). Hormones are routinely used for men whose cancer has spread locally to lymph nodes near the prostate, and they are being used increasingly often, together with radiation, for men

Michael Milken's Prostate Cancer

In 1993, Michael Milken, a forty-six-year-old former Wall Street financier, was diagnosed with prostate cancer. His PSA was 24, and cancer had already spread to his lymph nodes but not to his bones. He was immediately started on combined hormone therapy, consisting of both an antiandrogen and an LHRH agonist. Within six months, his PSA had fallen to 3, and he was given radiation treatment. Using continuing hormone treatment and strict dietary control, Milken's cancer has continued to remain in remission.

—adapted from Leon Jaroff, The man's cancer, Time, April 1, 1996

who have high-grade cancers (such as Gleason types 8, 9, and 10) that are likely to spread.

In men who have very large prostates, hormone treatment shrinks the prostate so that seed or beam radiation therapy will be more effective. Finally, hormones may be used as the only treatment for elderly men with prostate cancer who are unable or unwilling to undergo surgical or radiation treatments.

Men with low- and intermediate-grade prostate cancers are not thought to be viable candidates for hormone treatment. However, hormones are being used more and more frequently in such cases, despite the fact that no studies demonstrate that they are of any value. Some physicians start men on hormone treatment immediately after their diagnosis while the patients are deciding what definitive treatment they wish to have; the side effects of such treatment must be weighed against the dubious benefits of its use.

THE PROCEDURE

The earliest form of hormone treatment, removal of the testicles, can be done surgically on an outpatient basis. It is officially called an

Drugs Used for Hormone Treatment of Prostate Cancer

Antiandrogens (taken as pills) bicalutamide (Casodex) flutamide (Eulexin) nilutamide (Nilandron, Anandron) LHRH Agonists and Antagonists (given by injection) leuprolide (Lupron, Eligard, Viadur implant) goserelin (Zoladex) triptorelin (Trelstar) abarelix (Plenaxis)

orchiectomy, from the Greek word orchis, for "testicle." The procedure ensures that no testosterone will be available to stimulate prostate cancer cells. Its advantages include not having to take monthly injections, and its low cost compared to other forms of hormone therapy; its main disadvantage is that it is permanent and thus cannot be used like intermittent hormone therapy to decrease side effects. Historically, castration has been carried out for other reasons as well. Castrated men were called eunuchs in ancient Persia, India, and China and were put in charge of harems; often, they rose to governmental positions of high authority. Castrati have also been valued for their singing voices. Many men today elect methods of testosterone suppression other than orchiectomy for prostate cancer. Surgical castration is a deeply emotional issue for men, and there are very few harem positions available to provide consolation!

Antiandrogen drugs are taken orally. Flutamide (Eulexin) must be taken three times a day, but the others can be taken once daily. The LHRH agonists, by contrast, must be taken as injections, usually in the buttock. They can be given once a month or every three months; leuprolide (Lupron) has an additional formulation that can be injected every four months. A different formulation of leuprolide, Viadur, can be implanted under the skin and lasts for one year. Abarelix (Plenaxis) is an LHRH antagonist; its action is different from

Drug Costs

The following are approximate monthly costs of the hor

mone treatments commonly used for prostate cancer, as re

ported in 2004 by the Medical Letter (46:22-23). Many men

take both an LHRH blocker and an antiandrogen

In 2004,

Medicare decreased the reimbursement rate to doctors for

administering the LHRH blockers; the expense for patients

has increased accordingly.

Antiandrogens

bicalutamide (Casodex)

$417

flutamide (Eulexin)

$444

nilutamide (Nilandron, Anandron)

$344

LHRH blockers

leuprolide

Lupron Depot

$685

Eligard

$612

Viadur

$474

goserelin (Zoladex)

$470

triptorelin (Trelstar Depot)

$420

abarelix (Plenaxis)

$944

that of the agonists, but the results are the same. Because of serious side effects, it is given only to men who cannot take the other drugs. The cost of the antiandrogens and the LHRH blockers, several hundred dollars per month, is covered by most medical insurance plans. Some companies making these drugs have programs that supply them to men who are not covered by insurance.

In the past, diethylstilbestrol (DES) was used to suppress testosterone. It is no longer used because of its side effects. Ketoconazole (Nizoral) and megestrol (Megace) are occasionally used, and other drugs are being developed.

Many controversial issues exist with regard to how hormone treatments should be given. One debate concerns which is more effective, an antiandrogen or an LHRH blocker. Another addresses whether the two types of hormone treatment should be given together (as is commonly done) as a ''combined androgen blockade.'' Other issues include the optimal duration of treatment when using hormones at the same time as radiation treatment, and whether the hormone treatment is most effective if given before, during, or after the radiation treatment.

In addition, concerning hormone treatment for men whose surgical or radiation treatment has failed, it is debated whether hormone treatment should be started as soon as the PSA increases or whether it is better to wait until clinical or radiologic signs indicate that the cancer is actually spreading. There is also lively argument about whether hormone treatment should be intermittently stopped, to give the body a chance to recover, or whether it is most effective if given continuously. Intermittent hormone therapy consists of starting hormone treatment when the PSA exceeds, say, 4.0; continuing it until it falls below 1.0; then stopping until the PSA again exceeds 4.0. Preliminary studies suggest that intermittent therapy produces outcomes similar to continuous hormone treatment but with fewer side effects; therefore it is being increasingly used.2

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