Intermittent androgen suppression for prostate cancer: rationale and clinical experience

Research on hormonal treatments of prostate cancer over the past 20 y have focused on maximizing androgen ablation through combination therapy. Maxima l androgen ablation increases treatment-related side-effects and expense an d fails to prolong time to androgen-independent (AI) progression. The ratio nale behind intermittent androgen suppression (IAS) is based on: (1) observ ations that androgen ablation is palliative, not curative in most patients where quality of life must be considered; (2) assumption that immediate and rogen ablation is superior to delayed therapy in improving survival of pati ents with prostate cancer; and (3) the hypothesis that if tumor cells which survive androgen withdrawal are forced into a normal pathway of differenti ation by androgen replacement, then apoptotic potential might be restored a nd progression to androgen independence may be delayed. Observations from a nimal model studies suggest that progression to androgen-independence invol ves adaptive responses to androgen deprivation which are, in turn, modulate d by intermittent androgen replacement. Supported by these animal model observations, several centers have now test ed the feasibility of IAS therapy in non-randomized groups of patients with prostate cancer using serum PSA as trigger points. Experimental and clinic al data suggest that prostate cancer is amenable to control by IAS. IAS may offer clinicians an opportunity to improve quality of life in patients wit h prostate cancer by balancing the benefits of immediate androgen ablation (delayed progression and prolonged survival) while reducing treatment-relat ed side effects and expense. Whether time to progression and survival is af fected in a beneficial or adverse way is being studied in randomized, prosp ective protocols. The purpose of this article is to review the rationale be hind IAS, compare observations from published series, and discuss potential indications and treatment strategies using IAS.