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Treating Advanced Prostate Cancer

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Luteinizing hormone-releasing hormone (LHRH) analogs

Most patients who receive hormonal therapy choose LHRH analogs. These drugs work by decreasing testosterone production to very low levels by depleting the pituitary gland of the hormone needed to produce testosterone. However, before this decrease in testosterone occurs, patients experience a brief and temporary increase in testosterone production and tumor growth. This is due to a transient increase in release of LHRH from the pituitary gland with a resulting stimulation of testosterone production. This phenomenon, called tumor flare, can cause increased symptoms from the prostate cancer that didn't exist before the patient received the therapy. Some doctors prescribe antiandrogens (described below) to combat the symptoms caused by tumor flare. LHRH analogs are administered via injection or small implants placed under the skin. The most commonly used LHRH analogs in the U.S. are leuprolide  degarelix, triptorelin,and goserelin. They cause side effects similar to those from the surgical orchiectomy. These drugs carry a risk of triggering diabetes, heart disease, osteoporosis, and/or stroke. Before starting one of these drugs, patients should tell their doctor if they have a history of diabetes, heart disease, stroke, heart attack, high blood pressure, high cholesterol, or cigarette smoking.

Luteinizing hormone-releasing hormone (LHRH) antagonists

These drugs have been approved for use as endocrine therapy in patients with advanced prostate cancer. LHRH antagonists lower testosterone levels more quickly than LHRH analogs. In addition, they don't cause a tumor flare (temporary rise in testosterone levels) as do LHRH analogs. But they carry the risk of serious and potentially life-threatening allergic reactions. Such reactions may include low blood pressure and fainting, which indicate shock; swelling of the face, eyelids, tongue or throat; and asthma, wheezing, or other breathing problems. Patients who experience any of these reactions require immediate medical attention. Because of the small but serious threat that LHRH antagonists pose, their use is limited. Only patients with advanced, symptomatic prostate cancer who have no other treatment options or who refuse surgery can take them. Patients receive LHRH antagonists via injections into the muscles of the buttocks. To date, Plenaxis is the only LHRH analog approved for use in men with advanced prostate cancer. Other possible side effects include hot flashes, insomnia, pain, breast enlargement, breast pain or tenderness, back pain, constipation, or edema -- the buildup of fluids in the ankles and legs.

Antiandrogens for Prostate Cancer

These prostate cancer drugs work by blocking the effect of testosterone in the body. Antiandrogens are sometimes used in addition to orchiectomy or LHRH analogs.This is due to the fact that the other forms of hormone therapy remove about 90% of testosterone circulating in the body. Antiandrogens may help block the remaining 10% of circulating testosterone. Using antiandrogens with another form of hormone therapy is called combined androgen blockade (CAB), or total androgen ablation. Antiandrogens may also be used to combat the symptoms of flare (temporary rise in testosterone that occurs with the use of LHRH agonists). Some doctors  prescribe antiandrogen alone rather than with orchiectomy or LHRH analogs. Available antiandrogens include flutamide, biclutamide, and nilutamide. Patients take antiandrogens as pills. Diarrhea is the primary side effect when antiandrogens are used as part of combination therapy. Less likely side effects include nausea, liver problems, and fatigue. When antiandrogens are used alone they may cause a reduction in sex drive and impotence.

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