patients who respond to one anti-androgen are more likely to respond to the other two anti-androgens. Also, please keep in mind that each anti-androgen comes with some unique side effects and other concerns.
Bicalutamide is the easiest to take and the most effective at the lowest doses, but is known for having a higher rate of breast discomfort.
Flutamide is inexpensive, but it needs to be taken 2 to 3 times a day. It causes a higher rate of diarrhea and liver toxicity as compared to the other anti-androgens.
Nilutamide can, in rare situations, cause impaired night vision or lung inflammation (pneumonitis).
All of the above anti-androgens can be taken one after another, or in high doses (see chapter three), or not at all after your PSA rises on LHRH injections, or after surgery to remove the testicles.
OPTION 3 Anti-Androgen Withdrawal
Cancers can develop resistance to many medications in a somewhat similar way to how bacteria develop resistance to an antibiotic. This was acknowledged in 1992 when the concept of anti-androgen withdrawal (AAWD) syndrome was first recognized. It was found that, after a period of time on treatment with an anti-androgen pill, a tumor could actually use the drug to stimulate its own growth! Simply removing the anti-androgen when the PSA increase occurs has become a form of treatment (or non-treatment, really). Because the tumor can no longer use this specific anti-androgen as fuel, the PSA goes down. A PSA drop of 50 percent when an anti-androgen is removed is classified as a true AAWD. Only about 20 percent of men see a PSA benefit when going off the anti-androgen pill, but it still seems to be worth it for those who do respond.
Dosage No dosage needed; just remove the anti-androgen pill for several weeks. In the case of bicalutamide, the pill should be discontinued for longer (4 to 6 weeks).
Advantages A patient can get a treatment effect or a PSA reduction without doing anything except removing a pill from his daily regimen. It can usually be determined whether the patient is getting a benefit from AAWD within 6 weeks.
The catch You will need more frequent PSA testing and visits to the doctor after seeing a PSA increase (while you were on an anti-androgen).
What else do I need to know? AAWD can potentially be undertaken with any anti-androgen drug.
Although these minimal treatments may work for selected patients for a time, at some point additional therapies will likely be needed to manage the HRPC. Chapter three will discuss a variety of options that are generally referred to as secondary hormonal treatments.
Notes
After diagnosis with HRPC, you begin to consider a number of options with your physician. Several options exist in addition to the FDA-approved treatments for HRPC. Some of the most widely used medications for HRPC are the so-called “secondary hormonal treatments,” which work in a variety of ways. Some may even work by reducing testosterone below the accepted castrate level (to nearly 0 ng/dL). Regardless of how they act, you should be aware of these options.
Many doctors and patients like these secondary hormonal options, but interestingly they have never been approved for the specific purpose of prostate cancer treatment for men with HRPC. Why? It is probably because the drugs themselves were available for years for other purposes before doctors started to try them for HRPC. When the drugs were found to be effective for prostate cancer as well as the other purposes, there was no desire to recruit patients for an official clinical trial to exactly quantify their effectiveness, although it would have been better for patients to have such an official clinical trial completed.
Each secondary hormonal therapy has its own cost considerations. Some are inexpensive (estrogen, for example), and some are more costly (such as anti-androgen pills). Because doctors will use some of these options, we’ll discuss the advantages and drawbacks of each therapy. Keep in mind that a true response to a secondary hormone therapy is determined using a variety of tests, including one for PSA reduction, in the first few months of treatment (usually 3 months). The larger the response the better, for some patients. A 50 percent or more drop in PSA is outstanding, but a smaller response is also beneficial. A response to a secondary hormone treatment also may be determined using an imaging test, and even at times by considering a symptom reduction (less pain, for example). You can review with your doctor to determine whether a particular treatment is working for you.
Question: Why are adrenal glands so important to HRPC and the secondary hormonal treatments?
Answer: Other than the testicles, the human body makes androgens or male hormones in the adrenal glands (one of which sits on top of each kidney). The actual metabolic products that come from the adrenal gland hormones are known as “adrenal androgens,” or “androgen building blocks,” or “precursors” because they are used to make testosterone. Adrenal gland androgens include dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione. They all have the potential to continue to stimulate prostate cancer growth. Even if a patient has castrate levels of testosterone, it is known that adrenal gland androgens can at least weakly stimulate the androgen receptor (AR).
Thus, dietary supplements that should NOT be used when taking a secondary hormonal therapy include DHEA, DHEA-S, Tribulus Terrestis (which may have some DHEA-resembling compound in it), androstenedione, or any other supplement that claims to increase male hormone (testosterone) levels. Androstenedione is no longer sold over the counter, but there are still ways it can be obtained.
The problem with these supplements or compounds is that they can offset the impact of some of the secondary hormonal therapies as the treatments work better when the body has lower levels of these compounds. For example, new studies have shown better responses to anti-androgen drugs in individuals with lower DHEA blood levels. Therefore, be watchful for those compounds in supplements, and be sure always to check with your physician before taking a supplement.
CORTICOSTEROIDS
Corticosteroids are not considered to be true “secondary hormonal treatments” like the other drugs listed in this chapter. However, they are often given in conjunction with these drugs as well as a number of other HRPC treatments, so some information is being offered on them here.
Also known as glucocorticoids (generally); examples include: dexamethasone, hydrocortisone, prednisone, prednisolone, and methylprednisolone.
How is it taken? Usually as a pill, but can also be given by injection or intravenously (IV).
Dosage There is a variety of drugs and doses. It is not unusual to see patients taking 30 to 40 mg of hydrocortisone, or 10 mg or less of prednisone, or less than 1 mg of dexamethasone. Doctors are careful about the potency of these drugs.
Steroid Medication Review
Hydrocortisone—least
