Antiandrogen treatments in locally advanced prostate cancer: are they all the same?

Abstract

Purpose: The objectives are to review the published literature and to evaluate the weight of evidence for clinical effectiveness, safety, and tolerability of the currently available antiandrogens in the treatment of locally advanced prostate cancer. This article covers efficacy as monotherapy relative to castration and as adjuvant to radiotherapy and radical prostatectomy as well as adverse-effect and quality-of-life data.

Methods: The current literature from online databases between 1986 and the present, relating to antiandrogen treatments in men with locally advanced disease given either as monotherapy or as adjuvant to radical radiotherapy or prostatectomy, was reviewed. Antiandrogens researched included the non-steroidal antiandrogens, bicalutamide ('Casodex'), flutamide, and nilutamide, and the steroidal antiandrogen cyproterone acetate (CPA).

Results: The most comprehensively investigated and reported antiandrogen is bicalutamide, which has shown survival outcomes similar to those observed with castration in patients with locally advanced prostate cancer. In contrast, only limited clinical data are available for the other non-steroidal antiandrogens (flutamide and nilutamide) and the steroidal antiandrogen CPA in patients with locally advanced disease. In terms of safety and tolerability, CPA is associated with loss of libido and erectile dysfunction. CPA is also associated with cardiovascular risk and there have been occasional reports of fatal fulminant hepatitis and hepatocellular carcinoma. Gynecomastia is quite rare with CPA, which is in contrast to the non-steroidal antiandrogens. There are no direct comparisons between the three non-steroidal antiandrogens in terms of quality of life, but available evidence suggests that bicalutamide has a more favorable safety and tolerability profile than nilutamide and flutamide. Unlike CPA, non-steroidal antiandrogens appear to be better tolerated than castration, allowing patients to maintain sexual activity, physical ability, and bone mineral density, but these agents have a higher incidence of gynecomastia and breast pain (mild to moderate in > 90% of cases). Gynecomastia and breast pain, however, can be effectively managed.

Conclusions: The available evidence indicates that the different antiandrogens should not be regarded as equivalents in clinical practice and so the choice of treatment for patients with prostate cancer should be made on an individual basis. It is, therefore, important for clinicians to discuss the efficacy and tolerability profiles of all available treatment options with their patients to enable them to choose a treatment program that best fits with their lifestyle.

Fig. 1

Structures of the available steroidal (cyproterone acetate) and non-steroidal (bicalutamide, flutamide, nilutamide) antiandrogens

Fig. 2

Kaplan–Meier curve of overall survival following treatment with bicalutamide 150 mg versus castration in M0 patients (Iversen et al. 2000)

Fig. 3

Bar chart indicating the relative effects (maintenance vs. reduction) of bicalutamide 150 mg compared with castration on the following quality-of-life parameters: bone mineral density (Sieber et al. 2004), sexual interest (Iversen et al. 2000), and physical capacity (Iversen et al. 2000)