Luteinizing hormone-releasing hormone (LHRH) agonists for treatment of advanced prostatic carcinoma

Abstract

The identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.