ABSTRACT
Since the mid-1980s, research on hormonal treatments for prostate cancer have focused on maximizing androgen ablation through combination therapy. Unfortunately, maximal androgen ablation increases treatment-related side effects and expense and has not significantly prolonged time to androgen-independent (AI) progression. The rationale behind intermittent androgen suppression (IAS) is based on: 1) observations that androgen ablation delays tumor progression but is rarely curative in most patients, and hence quality of life must be considered; 2) the assumption that immediate androgen ablation is superior to delayed therapy in improving survival of patients with prostate cancer; and 3) the hypothesis that if tumor cells surviving androgen withdrawal can be forced along a normal pathway of differentiation by androgen replacement, then apoptotic potential might be restored, androgen dependence may be prolonged, and progression to androgen independence may be delayed. Observations from animal model studies suggest that progression to androgen independence involves adaptive responses to androgen deprivation, which are, in turn, modulated by intermittent androgen replacement.
