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Advances in the treatment of metastatic prostatic cancer.

Several exciting new forms of therapy for metastatic prostatic cancer have been introduced recently. Luteinizing hormone-releasing hormone (LH-RH) agonists paradoxically inhibit pituitary release of luteinizing hormone, resulting in a fall of serum testosterone to castrate levels within two to four weeks. These drugs have no cardiovascular side effects. A nonsteroidal antiandrogen, flutamide, may be as effective as orchiectomy in men with untreated metastatic disease and has the advantage of preserving potency in most men. In recent reports, combining the LH-RH agonist with an antiandrogen resulted in "total medical castration," which may substantially improve objective response rates and patient survival. Ketoconazole, an antifungal drug, also rapidly inhibits testicular and adrenal androgen synthesis and decreases plasma testosterone to castrate levels within 72 hours. In men with hormone-resistant disease, combination chemotherapy may produce an objective response rate of 50%. In men with severely painful bony metastasis, an inexpensive drug used in Paget's disease, etidronate disodium, may be palliative.