Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy.

RESULTS. All double-blind randomized and prospective clinical trials in advanced prostate cancer have shown that combination therapy using a nonsteroidal antiandrogen in association with a luteinizing hormone-releasing hormone (LHRH) agonist or orchiectomy has significant benefits according to all the subjective and objective parameters used, the most important being a prolongation of survival ranging from 5.4-15.0 months compared with LHRH agonists or orchiectomy alone (standard therapy). The benefits observed are probably the result of the blockade by the antiandrogenic agents of the androgens of adrenal origin, which represent, on average, 40% of the total androgens in men and which, otherwise, are left free to continue to stimulate prostate cancer after castration. These data are supported well by the demonstration of the expression of the genes encoding all enzymes required for the formation of active androgens in prostatic tissue from the inactive adrenal steroid precursors; this new specialty is called intracrinology. Both fundamental and clinical data indicate that low androgen levels cause changes in the cancer cells that lead to no or a poor response to antihormonal therapy. CONCLUSIONS. It is thus imperative that combination therapy be used as first treatment in all patients in whom endocrine therapy is indicated. Prior exposure to monotherapy shortens the patient's life by many months and produces a poor quality of life.