LHRH agonists

Question 0

Long Term Events

Answer 0

Osteoporosis
Clinical fracture
Obesity
Insulin resistance
Alteration in lipid 
Increased risk of diabetes
CV events

Question 1

Acute events

Answer 1

Tumor flare
Gynecomastia 
Hot flashes 
Erectile dysfunction 
Edema

Question 2

Agents

Answer 2

Goserelin (Zoladex)
Leuprolide (Lupron)
Triptorelin (Trelstar)

Question 3

Goserelin (Zoladex)

Answer 3

3. 6 mg SQ every 4 weeks

10. 8 mg SQ every 12 weeks

Question 4

Leuprolide

Answer 4

7.5 mg IM/SQ every month
22.5 mg IM/SQ every 3 months
30 mg IM/SQ every 4 months
45 mg IM/SQ every 6 months

Question 5

Triptorelin (Trelstar)

Answer 5

3. 75 mg IM every 4 weeks
4. 25 mg IM every 12 weeks
5. 5 mg IM every 24 weeks

Question 6

Anti androgens

Answer 6

Flutamide (Eulexin)
Bicalitamide (Casodex)
Nilutamide (Nilandron)

Question 7

Flutamide

Answer 7

250 mg tid
Diarrhea, Hematuria
Indicated in combo with a LHRH agonist

Question 8

Bicalutamide

Answer 8

50 mg daily
Diarrhea, hematuria
Indicated in combination of a LHRH agonist

Question 9

Nilutamide

Answer 9

300 mg daily x 1 month, then 150 mg daily

Diarrhea (low), disulfiram-like reaction, decreased visual accomodation, interstitial pneumonia

Question 10

Second Line Hormonal Therapy

Answer 10

Antiandrogen withdrawal
Corticosteroids 
Aminogluthethimide
Ketoconazole
Megestrol acetate
Gonadotrophin-releasing hormone (GnRH) antagonist

Question 11

Aminoglutethimide

Answer 11

Inhibits steroid synthesis in the adrenal gland
125mg po qid, increase to 250 mg qid
Cns lethargy (43%), skin rash (30%)
confusion, depression, dizziness, ataxia
p450 inducer
Corticosteroid replacement with hydrocortisone required

Question 12

Ketacolazole

Answer 12

Inhibits androgen synthesis in the testes and the adrenal gland, rapid onset
400 mg po q 8 h
N/v (33%), impotence, gynecomastia, dry skin, increased LFTs
Drug interaction with p450s
Corticosteroid replacement with hydrocortisone recommended but not required

Question 13

Megace

Answer 13

Inhibits release of LH, blockade of androgen receptor, and inhibition of 5-alpha reductase activity
40 mg po qid
Fluid retention, mild appetite stimulation

Question 14

Degarelix (Firmagon)

Answer 14

Alternative LHRH agonist
Degarelix binds to GnRH receptors on cells in the pituitary gland, reducing the production of testosterone to castrate levels
Advantage is speed and no need for antiandrogens

Question 15

Castrate Resistant Prostate Cancer

Answer 15

Docetaxel 75mg/m2 + prednisone 5 mg bid
Abiraterone (Zytiga)
Sipuleucel-T (Provenge)

Question 16

Aboratone (Zytiga)

Answer 16

Dose: 1000 mg daily with prednisone 5 mg twice daily. Empty stomach. (Food increases absorption)
Blocks cytochrome P450 CYP17 a critical enzyme in testosterone biosynthesis

Question 17

Sipuleucel-T (provenge)

Answer 17

Immunotherapy given every two weeks for 3 cycles
Adverse Events: chills, pyrexia, headache

Only considered for patients with metastatic CRPC and

1) no or minimal symptoms
2) good performance status
3) greater than 6 month life expectancy
4) no viceral disease

Question 18

Second line options

Answer 18

Abiraterone (zytiga) 
Cabazitaxel (jevtana) 
Mitoxantrone/prednisone
Docetaxel re-challenge
Salvage chemotherapy
Sipuleucel-T
Secondary hormone therapy
Clinical trial

Question 19

Enzalutamide (xtandi)

Answer 19

Blocks androgen binding and translocation of the androgen receptor
160 mg qd w or w/o food swallow whole
Fatigue, diarrhea, hot flashes, musculoskeletal pain and headache. Seizure in 0.6%
Avoid concomitant strong CYP 2C8
May decrease substrates of CYP 34A, 2C9, or 2C19

Question 20

Cabazitaxel (Jevtana)

Answer 20

Taxane derivative inhibits microtubules depolymerization

25 mg iv every 3 weeks in combination with prednisone
Premed with antihistamine, corticosteroid, and h-2 antagonist
Severe neutropenia, diarrhea, and febrile neutropenia
High 30 day mortality within last dose of drug