Types Of Hormone Therapy For Prostate Cancer
The overwhelming majority of patients get androgen deprivation by way of medical therapy, explains Moshe Ornstein, MD, a genitourinary medical oncologist at Cleveland Clinic Cancer Center.
Doctors use several types of medication to lower testosterone levels, but these therapies do so only temporarily. When you stop taking them, testosterone levels begin to rise again.
Here are some of the most commonly used hormone therapies.
Luteinizing hormone-releasing hormone agonists and antagonists LHRH is one of the key hormones released by the body before testosterone is produced. LHRH agonists and antagonists lower testosterone levels by blocking the release of LHRH. Treatment with these drugs is sometimes called medical castration because they lower androgen levels as much as orchiectomy, or removal of the testicles, does.
LHRH agonists and antagonists include:
- Vantas
- Firmagon
CYP17 inhibitors An LHRH agonist or antagonist can stop the testicles from making androgens, but other cells in the body still make small amounts of androgens. These small amounts of hormones can continue to stimulate cancer growth. A newer medication, Zytiga , blocks a key enzyme involved in androgen production called the CYP17 enzyme. Zytiga can be used to treat metastatic prostate cancer that has become resistant to traditional hormone therapies.
Traditional anti-androgens may be given along with LHRH agonists and antagonists. They include:
Results Of Treating Prostate Cancer With Hormone Therapy
Pamidronate to Prevent Bone Loss During Androgen-Deprivation Therapy for Prostate CancerMatthew R. Smith, M.D., Ph.D., Francis J. McGovern, M.D., Anthony L. Zietman, M.D., Mary Anne Fallon, L.P.N., Douglas L. Hayden, M.A., David A. Schoenfeld, Ph.D., Philip W. Kantoff, M.D., and Joel S. Finkelstein, M.D.
The purpose of this study was to determine whether a gonadotropin-releasing hormone agonist would prevent osteoporosis in men with prostate cancer. Here 47 patients with advanced or recurrent prostate cancer without bone metastasis were assigned to receive either leuprolide alone or leuprolide and pamidronate combined. Those who completed the study consisted of 41 patients. After 48 weeks physicians found substantial differences in bone mineral density between the two types of hormone therapies administered. Patients receiving leuprolide alone averaged a bone mineral density decrease of 3.3 percent in the lumbar spine, 2.1 percent in the trochanter, and 1.8 percent in the total hip. In contrast, patients treated with leuprolide and pamidronate experienced no significant bone mineral density changes at any skeletal site.
Alternative Antiandrogens to Treat Prostate Cancer Relapse After Initial Hormone TherapyKOJIMA, SATOKO SUZUKI, HIROYOSHI * AKAKURA, KOICHIRO SHIMBO, MASAKI ICHIKAWA, TOMOHIKO ITO, HARUO Journal of Urology. 171: 679-683, February 2004.
Will I Need To See My Doctor During And After Hormone Therapy
Yes, you will need regular medical checkups while getting hormone therapy. During these checkups your doctor will look at your medical history and give you a physical exam. Your checkup may include blood tests and imaging tests. For example:
- Some hormone therapy medicines can cause problems with your liver. So your doctor will watch your liver function with a blood test before you start treatment and at regular time points during the first four months of your treatment, and at regular times after that.
- Other hormone therapy medicines can cause you to get diabetes or become insulin resistant. In this case, your doctor may watch your blood sugar during your treatment. Insulin is a hormone produced by your body that helps change the food you eat into energy. When you are insulin resistant your body needs to make more and more insulin. Over time, this can cause you to have diabetes.
- Some hormone therapy medicines can increase your risk for cardiovascular problems. When your testosterone level drops your blood pressure and cholesterol may increase. This can put you at risk for cardiovascular problems such as a heart attack. Your doctor will watch your blood pressure and cholesterol.
- Your doctor will also check to make sure you dont have anemia. This is done with a simple blood test.
- Your doctor may also order a bone density test to check if you have osteoporosis.
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Hormone Therapy Helps Some Prostate Cancer Survivors Live Longer
A study published in the New England Journal of Medicine in January 2017 indicates that men whose prostates are removed to treat prostate cancer are likely to survive longer if they take drugs to block the male hormone testosterone in addition to undergoing radiation therapy.
Unfortunately, its not that simple.
Early History Of Hormonal Therapy For Prostate Cancer
The use of androgen deprivation as therapy for advanced prostate cancer began in 1941, when Huggins and Hodges first treated men with prostate cancer with either orchiectomy or estrogen. They monitored changes in prostate size and observed that improvements in acid and alkaline phosphatases were associated with cancer-related symptom relief. Largely due to the absence of other therapies, hormonal manipulation became a mainstay of treatment for symptomatic metastatic disease. Although it was originally hoped that suppression of testicular androgens would be curative, this proved not to be the case.
Although the testes are the primary source of testosterone, the adrenal glands also produce androgens. As a result, many patients with castrate levels of testosterone continue to have measurable levels of dihydrotestosterone in the prostate, thereby allowing continued stimulation of prostate cancer cells. The importance of adrenal androgens in prostate cancer was observed by Huggins and Hodges in their pioneering study, as many patients continued to have measurable levels of serum acid phosphatase, a surrogate marker of the disease, following medical or surgical castration. The authors considered this a clear indication that androgen production by the adrenal glands was ongoing.
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Diminution Of Muscular Strength
A mans muscular strength is reduced by 12% to 66% as the result of androgen deprivation. Moreover, muscle mass declines by 20% to 30% by age 70 . Because androgen deprivation reduces the amount of protein synthesis and the non-lipid body mass, obesity results. Thus, elderly patients should actively work against the loss of muscle by directed strength-training exercises .
Hormone Therapy: Immediate Versus Delayed
Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate Versus Deferred Treatment for Advanced Prostatic Cancer. British Journal of Urology 1997 79:23546. PMID: 9052476.
Messing EM, Manola J, Sarosdy M, et al. Immediate Hormonal Therapy Compared with Observation after Radical Prostatectomy and Pelvic Lymphadenectomy in Men with Node-Positive Prostate Cancer. New England Journal of Medicine 1999 341:17818. PMID: 10588962.
Messing EM, Manola J, Yao J, et al. Immediate Versus Deferred Androgen Deprivation Treatment in Patients with Node-Positive Prostate Cancer after Radical Prostatectomy and Pelvic Lymphadenectomy. Lancet Oncology 2006 7:4729. PMID: 16750497.
Nair B, Wilt T, MacDonald R, Rutks I. Early Versus Deferred Androgen Suppression in the Treatment of Advanced Prostatic Cancer. Cochrane Database of Systematic Reviews 2002 CD003506. PMID: 11869665.
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What Kinds Of Medicines Can Be Used To Lower My Testosterone
There are several types of medicines you can take to lower the amount of testosterone in your body. These are temporary ways to lower the amount of testosterone. When you stop taking these medicines, your testosterone level will begin to go up.
LHRH agonist
LHRH is a normal human hormone that tells your body to make testosterone. An LHRH agonist is a man-made hormone similar to the one made naturally in your body. LHRH agonists work like a light switch to shut off the production of testosterone in your body. When you are given this medicine, your body will stop making the LHRH hormone and your testicles will stop making testosterone. When you are first given this medicine, your body will continue to make testosterone for a couple of weeks. This means that your testosterone level may go up for a week or two and then begin to drop. This type of medicine works as well as having an orchiectomy . These medicines are given either monthly or every three months in a shot . The medicine may also be placed as small implants under your skin. The implant gives you a steady dose of medicine. Depending on the type of implant the medicine may last from one to 12 months.
Anti-androgens
Anti-androgens act like a brick wall. They block the small amount of testosterone made in your adrenal glands from reaching your prostate cancer cells. This keeps your prostate cancer cells from growing. These medicines are pills that are taken orally one to three times a day.
Whats The Typical Dosage
Hormone therapy can be used alone or in combination with other therapies. It may also be used before or after other therapies.
Lupron is administered by injection. The dosage will vary according to your particular situation. Here are some typical dosage options your doctor may prescribe:
- 1 mg once per day, varying the injection site
- 7.5 mg every 4 weeks
- 22.5 mg every 12 weeks
- 30 mg every 16 weeks
- 45 mg every 24 weeks
If you stop taking Lupron, youll start producing testosterone again.
You will experience some changes when your hormone levels fluctuate or have a substantial drop. Its a good idea to talk about this in advance so youre not caught off guard.
Consider asking some of these questions when you consult with your doctor:
- Why do you recommend treatment with Lupron?
- How often will I have to take the drug?
- Will I administer it myself or will I need to come in to the clinic?
- How often will we test to see if its working?
- How long will I have to take it?
- What should I do if I miss a dose or if I stop taking it?
- What are the potential side effects, and can we do anything about them?
- Are there any other medications, supplements, or foods I should avoid while taking Lupron?
- If it doesnt work, what are the next steps?
According to the American Cancer Society, the relative five-year survival rates for men with prostate cancer, compared to men without the disease, are:
Your doctor can give you an idea what to expect from your treatment with Lupron.
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Secondary Treatment Following Relapse
Hormone therapy may also be used as a secondary or salvage treatment when PSA levels rise following initial prostate cancer treatment, indicating the cancer has returned. This situation is known as biochemical recurrence. The salient points to keep in mind are that hormone therapy is most often used as a salvage treatment when PSA doubling time is less than six months, indicating that the cancer is aggressive or may have already metastasized.
What Does Current Guidance Say On This Issue
NICE prostate cancer guidelines give recommendations for locally-advanced and metastatic prostate cancer, which fall under the advanced definition used in this review.
Radical radiotherapy plus androgen suppression therapy is recommended for high-risk localised cancer. NICE advises that suppression may be given before, during or after radiotherapy, but dont state a precise timing in relation to diagnosis. Chemotherapy plus androgen suppression is recommended for newly diagnosed metastatic prostate cancer.
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Hormonal Therapy Treatment For Prostate Cancer
The following article contains a good deal of technical information, but we feel the information is helpful and would be of interest to many of our QUEST readers.
Hormonal therapy is most often used after both a radical prostatectomy and radiation have failed. Sometimes, however, it is used as a primary therapy in older patients who would not tolerate surgery or radiation.
Hormonal therapy can be divided into two phases, primary and secondary.
Primary
Most prostate cancer cells either die or go into a dormant phase when the male, blood hormonal level level is dramatically lowered. This phase of so-called androgen-dependent prostate cancer can be quite variable, lasting from only a few months to as long as 18 years. Male hormone levels can be lowered or rendered less effective in various ways.
One method of lowering the testosterone level is by removal of the testicles . Another is by injections called Lupron or Zoladex . A third alternative is antiandrogen pills such as Megace , Eulexin , Casodex , Nilandron .
Other methods are by estrogens by inhibitors of androgen synthesis, such as ketoconazole by antiestrogens, such as tamoxifen by herbal estrogen compounds, such as PC spes or by glucocorticoids .
Secondary
The principle behind secondary hormonal therapy is that while the patient is taking a hormone that blocks the growth of the cancer, the cancer cells can mutate or change in a way that makes the Eulexin stimulate their growth.
Hormone-Resistant
Hormonal Therapies For Advanced Prostate Cancer Linked To A Higher Risk Of Falls And Fractures
- By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
Falls rank among the top causes of death and injuries among the elderly, and the risk increases significantly in older people being treated for cancer. Now, investigators are reporting that a newer class of drugs for advanced prostate cancer is associated with a significant increase in fall risk.
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Combination Chemotherapy And Hormonal Therapy For Advanced Prostate Cancer
Alternative and additional therapies in patients with hormone refractory, metastatic, and locally advanced disease have been investigated in an effort to improve survival. Despite poor outcomes in the past, the availability of new chemotherapeutic agents has resulted in renewed interest in chemotherapy for advanced prostate cancer. A recent study by Wang and colleagues examined the role of mitozantrone as an adjuvant to hormonal treatment in men with locally advanced prostate cancer. Ninety-six patients were entered into a stratified, randomized single institution study of hormonal therapy with an LHRH agonist and flutamide with or without 4 cycles of adjuvant mitozantrone. The results show that patients with localized prostate cancer receiving chemotherapy had a higher initial objective response rate and longer median survival than patients treated with hormonal therapy alone. The study demonstrated no advantages to chemotherapy in patients with metastatic disease. There were insignificant advantages to chemotherapy in overall response rates and PSA responses . There was no difference between the patient groups in time to treatment failure.
Hormonal Therapy For Aggressive Prostate Cancer: How Long Is Enough
- By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
Men weighing treatment options for intermediate- or high-risk cancer that is still localized to the prostate can face a tricky question. A standard approach in these cases is to give radiation to the prostate along with drugs that block testosterone, a hormone that makes the cancer cells grow faster. For how long should this hormone therapy last? Thats not entirely clear. The drugs have side effects, such as fatigue, impotence, and a loss of muscle mass. But radiation doesnt control prostate cancer effectively without them. Doctors therefore aim to give hormone therapy only for as long as it takes to help their patients, without causing any undue harm.
Now, newly published results from a phase 3 clinical trial are providing some needed guidance.
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How Might I Feel During Hormone Therapy
Nearly all men being treated for prostate cancer say that they feel emotionally upset at different times during their hormone therapy. It’s not unusual to feel anxious, depressed, afraid, angry, frustrated, alone, or helpless. Hormone therapy may affect your emotions because it lowers the amount of testosterone in your body.
Some men find it helps to learn about their disease and treatment because it makes them less afraid of their treatment. Find out as much as you want to know. Do not be afraid to ask questions. Your emotional health is as important as your physical health.
Talking with an understanding friend, relative, minister or another patient may be helpful. Your doctors office may be able to give you a list of local prostate cancer support groups. There will be men in the support groups who have had hormone therapy. You may also contact the American Cancer Society at 1-800-227-2345 or the National Cancer Institutes Cancer Information Line at 1-800-422-6237 to find out about cancer resources in your local community.
Many people don’t understand prostate cancer or its treatment. They may stay away from you because they’re not sure what to say or how to help. Try to be open when you talk to other people about your illness, treatment, needs, and feelings. People will often be willing to lend their support. If you get tired easily, limit your activities and do only the things that mean the most to you.
Treatment To Lower Androgen Levels From The Adrenal Glands
LHRH agonists and antagonists can stop the testicles from making androgens, but cells in other parts of the body, such as the adrenal glands, and prostate cancer cells themselves, can still make male hormones, which can fuel cancer growth. Drugs are available that block the formation of androgens made by these cells.
Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.
Abiraterone can be used in men with advanced prostate cancer that is either:
- High risk
- Castrate-resistant
This drug is taken as pills every day. It doesnt stop the testicles from making testosterone, so men who havent had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone needs to be taken during treatment as well to avoid certain side effects.
Ketoconazole , first used for treating fungal infections, also blocks production of androgens made in the adrenal glands, much like abiraterone. It’s most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.
Ketoconazole also can block the production of cortisol, an important steroid hormone in the body, so men treated with this drug often need to take a corticosteroid .
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