Metastic & refractory disease androgen synthesis inhibtors

Question 1

What enzymes play a critical role in androgen synthesis ?

Answer 1

• cyp 450

Question 2

what is cyp17A1 inhibition

Answer 2

prevents pregnenolone —x–> DHEA (precursor testos)

Question 3

Abiraterone acetate

Answer 3

• poten + specific inhibitor CYP17A1 = reduce testos + ADT
• • ADT = effective initial therapy hormone-sensitive PCa + mCRPC
• inhibit CYP1A17:
  1. MA excess - fluid retention, hypok , HT
  + prednisone BD
  = adm empty stomach
  1hr before/ 2hrs after meal = food increases absorption

Question 4

Ketoconazole

Answer 4

• symptomatic relief
  400mg PO tds
• a/e - diarrhea, increase LFT/RFT, hypoadrenalism
• absor requires gastric acidity - avoid H2 blockers, PPIs / antacids
  + hydrocortisone = prevent symptomatic hypoadrenalism

Question 5

improve survival mCRPC

Answer 5

chemo + docetaxel + prednisone

Question 6

improve survival mCRPC/ progressed / intolerant to docetaxel

Answer 6

chemo + carbazitaxel + prednisone