Experimental use of GnRH antagonists as second-line hormonal therapy.

The hypothesis that follicle-stimulating hormone (FSH) signaling contributes to the progression of androgen-independent prostate cancer (AIPC) is supported by preclinical evidence. Therefore, abarelix, a gonadotropin-releasing hormone antagonist that suppresses circulating FSH more effectively than standard hormone therapies, would be expected to reduce FSH without altering testosterone, thereby testing the hypothesis that circulating FSH supports the progression of AIPC. The authors tested abarelix on 2 groups of men with early AIPC: 1 group had undergone luteinizing hormone-releasing hormone agonist therapy and the other had undergone orchiectomy. Although there was no confirmed response in either group, the investigators found the time to progression, fraction of patients progression-free at the end of therapy, and fraction of patients with confirmed prostate-specific antigen reductions less than 50% were all higher in the orchiectomy-treated patients. This hypothesis-generating observation has led to a phase I trial to determine whether an escalation in the dosage of abarelix is safe and will produce more complete suppression of FSH.