The antiandrogen withdrawal syndrome

Area of Science:

• Oncology
• Pharmacology
• Urology

Background:

• The unanticipated agonist effect of antiandrogens on LNCaP prostate cancer cells was first observed in 1989.
• A phenomenon termed 'flutamide withdrawal syndrome' was described, characterized by decreased prostate-specific antigen (PSA) levels after flutamide cessation.
• This paradoxical response to antiandrogens has since been reported for other drugs like bicalutamide and chlormadinone acetate, leading to the broader term 'antiandrogen withdrawal syndrome'.

Purpose of the Study:

• To investigate the phenomenon of antiandrogen withdrawal syndrome.
• To explore the potential mechanisms underlying the paradoxical response to antiandrogens.
• To highlight the clinical significance of withdrawal therapy in managing hormonally relapsed prostate cancer.

Main Methods:

• Review of clinical observations and reported cases of antiandrogen withdrawal syndrome.
• Discussion of proposed molecular mechanisms, including androgen receptor mutations and direct drug effects.
• Analysis of the clinical implications for treatment strategies in advanced prostate cancer.

Main Results:

• The antiandrogen withdrawal syndrome is a recognized clinical event in prostate cancer treatment.
• Several potential mechanisms, including androgen receptor alterations, are hypothesized but not fully elucidated.
• Withdrawal therapy has shown efficacy in some patients with relapsed prostate cancer.

Conclusions:

• The exact molecular mechanism of antiandrogen withdrawal syndrome remains unclear.
• Withdrawal therapy is a crucial consideration for patients with hormonally relapsed prostate cancer.
• This approach should be attempted before resorting to more toxic therapeutic options.