as Non-steroidal anti-androgens, including bicalutamide, flutamide, and nilutamide. Steroidal anti-androgens include megestrol acetate (Megace) and cyproterone acetate (Androcur).
How is it taken? pill.
Dosage Dosages vary by drug and situation. Commonly used are bicalutamide in low to high doses (50 to 150 mg/day), flutamide (a range of doses), nilutamide (150 to 300 mg/day), and cyproterone acetate (in some countries such as Canada, 100 to 200 mg a day).
Advantages Simple to take. There are now some generic options, so check the price, please. Can have some effectiveness when given in higher doses for HRPC patients, especially when used in the early stages of HRPC. If someone responds quickly to one non-steroidal anti-androgen, he is more than likely to respond to the other two after that one anti-androgen is no longer effective.
The catch Non-steroidal anti-androgens are used for treatment of the cancer itself (in high doses) or along with other medications (LHRH), but steroidal anti-androgens are really just used today for treating side effects of ADT, such as hot flashes, and not commonly used to treat HRPC.
What else do I need to know? These drugs directly bind to and block the androgen receptor (AR).
Steroidal anti-androgens (cyproterone acetate and megestrol acetate) are known for having progesterone-like (female hormone-like) activity, which is why they are more commonly used to treat hot flashes from ADT (LHRH). They also have side-effect issues such as impact on sexual function, weight gain, fluid retention (edema), nausea, and a slight risk of blood clots. Cyproterone acetate has also been found to potentially increase the risk of heart disease.
Non-steroidal anti-androgens (bicalutamide, flutamide, and nilutamide) are more specific and selective for the AR, so there is a lower incidence of side effects. Research suggests that there is a good chance a patient will respond to an anti-androgen if he has already responded well to ADT or a previous anti-androgen.
KETOCONAZOLE
Also known as Nizoral.
How is it taken? pill.
Dosage 200 to 400 mg three times a day (a total of 600 to 1200 mg per day).
Advantages Arguably, the most popular currently available second-line hormonal treatment, and one of the most effective. Ketoconazole is also one of the least expensive drugs used to treat prostate cancer.
The catch Side effects are a concern. There have been many noted because this is also one of the best-studied secondary hormonal therapies. Side effects include: sticky skin, easy bruising, dry skin, liver toxicity, nausea and vomiting, breast enlargement and tenderness, fatigue, swelling (edema), and rash. Zytiga may soon replace this drug (see chapter six).
Question: How should I take my ketoconazole to make it the most effective?
Answer: Ketoconazole is absorbed much better in an acidic environment, so individuals taking antacids or any acid-suppressive over-the-counter or prescription medicine (H2 blockers or proton pump inhibitors, for example) will have trouble absorbing these pills.
Thus it is advised to take the pills with something acidic regardless of whether or not you are on an acid-inhibiting medication. For example, soda pop (regular or diet cola) is acidic and works well. The more popular recommendation is to take between 250 and 500 mg of ascorbic acid, also known as vitamin C, with each dosage. One word of caution is to avoid “pH neutral” or “buffered” vitamin C, as these have been formulated to be non-acidic and won’t assist in absorbing ketoconazole. Please make sure you buy inexpensive “ascorbic acid” or plain old vitamin C when taking it with ketoconazole. It should say only ascorbic acid on the ingredient label.
Also, do NOT take ketoconazole with grapefruit or grapefruit juice. Avoid other citrus and exotic fruit juices as well. Grapefruit particularly has the ability to block a protein in the gut (P-glycoprotein) and liver (CYP3A4), where approximately half of all prescription medications are metabolized. What does this mean? Consuming grapefruit (and possibly some other juices) may actually raise the level of exposure to ketoconazole in the body and cause more side effects. In addition, ketoconazole itself is similar to grapefruit in that it blocks the ability of the liver enzymes (CYP3A4) to metabolize a variety of drugs (cholesterol-lowering drugs or statins and some antibiotics, for example). This means that ketoconazole can increase your level of exposure to some other drugs (almost half of those on the market), and thereby increase your chance of side effects from them. For example, it can increase the risk of liver toxicity and muscle or joint discomfort from taking a cholesterol-lowering drug (statins). Generally speaking, you have to be careful what you eat and drink with ketoconazole. Also, you need to be mindful of what effect ketoconazole can have on other prescription medications you are currently taking.
This drug enzymatically inhibits the production of adrenal androgens, but it is not specific for adrenal androgens only, so it usually requires corticosteroid replacement to prevent adrenal problems. Often prescribed is 20 to 30 milligrams of hydrocortisone in the morning and 10 milligrams in the evening, or some variation of this regimen.
Higher androstenedione levels are predictive of a less-than-adequate response to ketoconazole, which further shows that this drug works by inhibiting adrenal androgen synthesis. Some doctors may want to measure androstenedione levels and, if they are high, consider a higher dosage, another treatment method, or another secondary hormonal treatment.
Working closely with your doctor is critical in avoiding any issues as you begin to take ketoconazole.
What else do I need to know? Ketoconazole has been used medically for a variety of purposes. It is a well-known synthetic anti-fungal drug, used to prevent skin and fungal infections (athlete’s foot and ringworm) and is even effective in individuals with suppressed immune systems. It is also sold over the counter and as a simple prescription in very low doses (1 to 2 percent) as an anti-dandruff shampoo. It is sold as a topical cream and even an oral tablet.
This drug is very effective at reducing male hormone production and other hormones in the adrenal glands. It can reduce testosterone levels and thus has even been used in the past to prevent post-operative erections. Clinical research suggests that this drug is effective at killing some HRPC. Previous clinical research has suggested as many as 50 percent of men get some kind of response to this drug.
Ketoconazole accumulates or is absorbed by fatty tissue, which is one of the reasons it has more side effects as compared to newer anti-fungal medicines (fluconazole and itraconazole). However, this absorption also explains why it is more effective with cancer: because it can penetrate a lot of barriers.
The average dosage is 400 mg every 8 hours (1200 mg total for the day). However, this dosage causes a number of the side effects listed above. Other studies have demonstrated that by starting with 200 mg every 8 hours (600 mg total for the day) you can reduce the side effects, but the drug is still almost as effective.
Question: Why does it have to be taken every 8 hours?
Answer: The drug is rapidly destroyed by the liver and, therefore, does not remain at an effective dosage in the blood for a long period of time. It is said to have a short half-life. For this reason, it must be taken at least every 8 hours to give optimal results.
SANDOSTATIN
Also
