Androgen Withdrawal Phenomenon

Androgen Withdrawal Phenomenon

Urology relation: Treatment of Prostate cancer

Definition: 
A decrease in PSA level after withdrawal of antiandrogens from patients showing objective responses to combination therapy (LHRH agonist and antiandrogens)

Drugs:

1.      Flutamide

2.      Bicalutamide

3.      Nilutamide

4.      cypertrone acetate

5.      DES

6.      Progestational agents

PSA decline phenomena

-        Time: within 4 to 6 wks

-        Amount: up to 50 % (in 15 to 30%)

-        Duration: 3.5 - 5 months

Explanation:

Mutation of AR that make antiandrogen act an agonistic function.

Evidence:

-        (Suzuki; 1996) A Point mutation of AR in PCa cell line that allow flutamide to increase proliferation was found in PCa sample of PCa from patients with AWP .

-        (Hara; 2003) similar point mutation found in cases have Bicalutamide act as agonist.

-        (Bohl; 2005) X ray crystallography shows that bicalutamide bind to mutant AR just like DHT bind to nirmal AR.

Applications:

1.   Associated measurable tumor response: not common

2.  Overall survival: not affected

3.  Act a confounding effect on clinical trials

4.  Predictors: those with rapid response of PSA after androgen ablation.

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Ahmed Bakr, MD, FEBU

Egypt