|
|
|
Stephan L. Werner, M.D., F.A.C.S. Hormonal Therapy is based on the fact that prostate cancer cells frequently use the male hormone, testosterone, as "fertilizer", and the absence of testosterone leads to the death or weakening, (apoptosis), of many, but not all, prostate cancer cells. As a result, many patients with incurable prostate cancer, (Stage D and late Stage C), can have their life extended and quality of life improved by the use of hormonal therapy. There are two sources of testosterone in the body, the testes, and the adrenal glands. Originally, removal of the testicles, (castration), was the only treatment for late stage prostate cancer, and to this day it remains the most cost effective and patient compliant form of treatment. There are several injectable medicines, LHRH agonists, (Lupron, Zoladex, Eligard, Viadur, Trelstar or Vantas), and LHRH antagonists, (Plenaxis) which block the production of testosterone by the testes, and are given at varying intervals, from 1 to 12 months, depending on the drug and dosage. Some of the longer acting forms are implanted either through a needle or a tiny incision. They are not inexpensive. Interestingly after several years of LHRH therapy the testes turn off and the medication may be discontinued for a period of time without or with very delayed return of testosterone levels. Plenaxis, because of its rapid decrease in testosterone levels without the flare seen with LHRH agonists, has a special use in starting hormonal therapy in patients with painful metastases, impending spinal collapse or urinary obstruction. There are several oral medications, antiandrogens, (Nilandrone, Casodex, and Eulixin) that block the effect of testosterone on prostate cancer cells,. Unfortunately, they are not totally effective when the testes are functioning so these drugs are infrequently used alone, although such "monotherapy" may be occasionally appropriate. There is some data that supports the use of high dose Casodex as monotherapy. Frequently LHRH inhibitors or castration and antiandrogens are combined into Total Androgen Blockade/ Combined Androgen Blockade, CAB, the most aggressive form of hormonal treatment used for advanced prostate cancer. A common side effect of hormonal therapy is hot flashes, due to hormone deficiency. As in female menopause the frequency and intensity of attacks vary widely. For those who find the hot flashes intolerable they may be treated with Megace, Depo-Provera which is injectable, or perhaps low dose estrogen, DES, therapy. Other side effects of hormone therapy can be weight gain, erectile dysfunction, decrease in muscle mass and strength, personality changes, decreased mentation and osteoporosis. Patients on hormone therapy should get dexa-scans for osteoporosis every one to two years. It is advisable for patients on hormone therapy to take calcium, 500 mg/day and Vitamin D, 400 units/day, under the guidance of a physician. In some patients bisphosphonates such as fosamax or zometa may be indicated to prevent or counteract osteoporosis. Although it make take many years, hormonal therapy will eventually fail, as there are cancer cells that are or become "hormone resistant". In an attempt to improve results there are several research protocols being done to assess the use of early chemotherapy combined with androgen blockade. Sometimes an alternate antiandrogen, ketokonazole, may give a temporary response. Chemotherapy has in general not had excellent results in late stage prostate cancer, but searches for an active combination continues. These trials are frequently in combination with Combined Androgen Blockade. Occasional patients respond well. Mitoxantrone and prednisone has some promise in slowing down the disease and/or relieving pain in patients with painful bony metastases. Trials with taxotere or tamoxiphen sometimes combined with estramustine have also shown responses in a significant number of patients. Thalidomide is also under study. There are many clinical trials with other drugs being carried out at many centers including ours. In very late stage prostate cancer the cancer cells may become "hormone resistant", and the cancer progresses. It has been found that in some patients "cycling" the antiandrogens on and off over several months, has induced positive responses. Estrogens, or female hormones not only suppress the production of testosterone but also have a negative effect on prostate cancer cells and are sometimes used in cases of hormone resistant cancer or sometimes as early therapy. Unfortunately, high dose estrogens have been shown to cause increased blood clotting, leading to clots, heart attacks, strokes and vascular accidents. DES, diethylstilbestrol, is still used in some patients. Occasionally it is used in low dose in patients with hormone resistant prostate cancer with some response. PC-SPES, an alternative medicine, no longer available, probably works due to its estrogenic effects. A snake oil special!! It turns out this "miracle" drug was seeded with DES or estrogen, an old and well known treatment for prostate cancer, with blood clotting problems. When someone stopped the estrogen supply, the "successes" disappeared. Subsequently relatives of coumadin, a blood thinner and valium were found in some bottles. The FDA removed it from the market. There has also been some interest of late in intermittent hormone therapy, where the LHRH is cycled on and off either on a timed cycle, or based on PSA response. No long term data is yet available as to efficacy. Neo adjuvant therapy is the pretreatment of prostate cancer with hormonal therapy. By pre-treating the prostate cancer with testosterone deprivation many cancer cells will be killed and others will be weakened and will die more easily after radiation. Short term data supports improved long term results, but the final answer is not in. To induce hormone deprivation, oral and/or injectable medication is given for 2 to 8 months before starting therapy, during the radiotherapy and for two months afterwards. The hormonal therapy also helps keep the cancer in check during this time. There is considerable debate whether neoadjuvant therapy before surgery might improve the results as well, While early results were not promising, later results suggest some improvement. Occasionally, if there is a need to delay radical prostatectomy for a period of several months, use of short term hormone treatment may be appropriate.
Rev:04/05 Stephan Werner, M.D., F.A.C.S. |
|
[Home] Werner - Francis Urology Associates llc - Mid Atlantic Urology Associates llc Greenbelt - Bowie - Laurel Maryland (301) 441-8900 Fax (301) 982 0453 7500 Hanover Parkway Suite 206 Greenbelt, MD 20770
Rev:03/08 |